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Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model

  • Liya Song and Lihua Li EMAIL logo
Published/Copyright: December 31, 2024
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Open Life Sciences
From the journal Open Life Sciences Volume 19 Issue 1

Abstract

This study aimed to investigate the differential expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in relation to the Toll-like receptor (TLR)/nuclear factor κB (NF-κB) signaling pathway in an obese rat model. A total of 200 8-week-old male Wistar rats were randomly assigned to a control group (Ctrl, n = 40) and an observation group (Obs, n = 160), with obesity induced through a high-fat diet. Following modeling, the Obs group was further divided into a model group, a PI3K/AKT inhibition group, a TLR/NF-κB inhibition group, and a combined PI3K/AKT + TLR/NF-κB inhibition group, with 40 rats in each. Metabolic changes were assessed by monitoring the glucose infusion rate (GIR), as well as conducting an intraperitoneal glucose tolerance test (IPGTT) and an intraperitoneal insulin tolerance test (IPITT). Hematoxylin and eosin staining was utilized to observe morphological changes in adipose tissue, while Western blotting was employed to detect the expression levels of proteins associated with the PI3K/AKT and TLR/NF-κB signaling pathways in adipose tissue. The results indicated that the Obs group exhibited significantly higher blood glucose and insulin levels during the IPGTT and IPITT experiments compared to the Ctrl group (P < 0.05). Additionally, the GIR, as well as the expression levels of p-PI3K and p-AKT proteins in the Obs group, were significantly lower than those in the Ctrl group (P < 0.05). In both the PI3K/AKT inhibition group and the combined PI3K/AKT + TLR/NF-κB inhibition group, the expression of relevant proteins further declined (P < 0.05). These findings suggest that while a high-fat diet decreases the activity of the PI3K/AKT signaling pathway, it concurrently promotes inflammatory responses by upregulating the TLR-4 and NF-κB signaling pathways, indicating a critical role for these pathways in obesity-related metabolic abnormalities.

Graphical abstract

This study investigated the effects of activation and inhibition of the PI3K/AKT and TLR-4/NF-κB signaling pathways on insulin resistance in a high-fat diet-induced obese rat model. The results indicate that a high-fat diet can activate these signaling pathways by regulating the expression of related proteins, affecting metabolic health. Rat PI3K/AKT pathway protein.

Keywords: obesity rat model; high-fat diet; phosphatidylinositol-3-kinase/protein kinase B; Toll-like receptor/nuclear factor kappa B; differences; expression

1 Introduction

In recent years, the accelerated process of urbanization globally has led to significant changes in lifestyle and dietary habits, resulting in obesity becoming a global public health issue, with a particularly sharp increase in obesity rates in China [1,2,3]. Obesity is not only a major contributor to various metabolic diseases but is also closely associated with a range of health issues, including cardiovascular diseases, diabetes, and fatty liver. Epidemiological studies indicate a significant association between obesity and type 2 diabetes. In obese states, adipocytes in adipose tissue undergo hypertrophic apoptosis, accompanied by substantial cell death, which triggers a strong stress response in the immune system and induces chronic inflammation in the body [4,5,6]. Although a direct causal relationship between inflammation and type 2 diabetes has yet to be clearly established, increasing evidence suggests that chronic inflammation may be one of the key drivers in the onset and progression of diabetes.

Adipose tissue, as the largest energy storage organ in the human body, plays a crucial role in regulating energy metabolism and maintaining energy balance. However, in the context of obesity, dysfunction of adipose tissue leads to systemic metabolic disturbances, which can subsequently trigger chronic inflammation and insulin resistance (IR). The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is a key intracellular signaling pathway that transmits various critical cellular signals and is involved in processes such as cell proliferation, differentiation, metabolism, and apoptosis [7,8,9]. The PI3K/AKT signaling pathway plays a central role in insulin signaling by promoting glucose uptake and utilization, thereby maintaining glucose homeostasis. Additionally, the PI3K/AKT signaling pathway directly influences insulin sensitivity by inhibiting apoptosis and promoting cell survival. Therefore, abnormal activation or inhibition of the PI3K/AKT signaling pathway may represent a significant mechanism underlying obesity-related metabolic diseases. Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and are widely expressed on the surface of immune cells. Activation of TLRs can initiate various signaling pathways, leading to the expression of inflammatory cytokines and mediating innate immune responses [10,11,12]. Recent research revealed that TLRs play not only a critical role in antimicrobial defense but also a significant role in the development and progression of chronic inflammation and metabolic diseases. In particular, during obesity-associated chronic low-grade inflammation, TLRs exacerbate IR and accelerate the onset of type 2 diabetes by activating signaling pathways such as nuclear factor κB (NF-κB), which promotes the production of inflammatory cytokines. NF-κB is a transcription factor widely present in eukaryotic cells, initially discovered in B lymphocytes. NF-κB regulates the expression of various genes associated with immune responses and inflammation by specifically binding to regulatory elements in target genes [13,14,15]. It plays a central role in cellular stress, immune responses, inflammation, and cell survival. The PI3K/AKT signaling pathway acts as an upstream regulator of NF-κB, modulating its activity through multiple mechanisms. For instance, the PI3K/AKT pathway can indirectly enhance NF-κB activation by inhibiting the degradation of NF-κB inhibitor proteins (IκB), thereby promoting NF-κB nuclear translocation and activation, which exacerbates inflammation and IR. Khatua et al. reported that PI3K-mediated NF-κB pathway activation induces the expression of anti-apoptotic proteins, further driving the persistence and chronicity of inflammatory responses [16].

Based on the aforementioned background, this study aimed to construct an obese rat model to investigate the expression changes of the PI3K/AKT and TLR/NF-κB signaling pathways under obesity and their roles in obesity-related metabolic diseases. By employing intraperitoneal glucose tolerance tests (IPGTT), intraperitoneal insulin tolerance tests (IPITT), hematoxylin and eosin (HE) staining, and Western blot analysis, this study systematically examined the expression changes of proteins associated with the PI3K/AKT and TLR/NF-κB signaling pathways in the obese rat model and explored their relationship with IR and chronic inflammation. The results were expected to provide new theoretical insights into the mechanisms of obesity-related metabolic diseases and offer references for developing targeted therapeutic strategies.

2 Materials and methodologies

2.1 Experimental animals

This study utilized 200 8-week-old specific pathogen-free male Wistar rats (weight 180–200 g), purchased from Beijing Luhe Hospital Affiliated to Capital Medical University. The rats were housed in standard conditions prior to the experiment. They were acclimated for 7 days in an environment with a relative humidity of 55 ± 5%, a constant temperature of approximately 25°C, and a 12-h light/dark cycle, with a standard diet and ad libitum water. After the acclimation period, rats exhibiting normal activity were selected for subsequent experiments. Throughout the study, strict adherence to the “3Rs” principle – reduction, reuse, and recycling – was maintained to minimize the number of animals used and to alleviate pain while ensuring research objectives were met. Additionally, all experimental procedures followed animal welfare and humane care guidelines.

  1. Ethical approval: The research related to animal use has been complied with all the relevant national regulations and institutional policies for the care and use of animals. The research protocol was approved by the local Ethics Committee (Approval No: 202062), which confirmed the scientific validity and ethical compliance of the study.

2.2 Construction and grouping of obesity rat models

This study established an obese rat model with IR induced by a high-fat diet (5.4 kcal/g, with fat content up to 46.5%). At the start of the experiment, all rats were randomly assigned to the control group (Ctrl group, n = 40) and the observation group (Obs group, n = 160). The Ctrl group was fed a standard diet (3.8 kcal/g, fat content 10%), while the Obs group received a high-fat diet. After 8 weeks of feeding, the rats’ body weight and anogenital distance were measured, and Lee’s index (Lee’s index = (body weight × 1,000)1/3/anogenital distance) was calculated to assess the degree of obesity. For the rats in the Obs group, insulin sensitivity was measured using the high-insulin euglycemic clamp technique, and rats meeting the obesity criteria based on Lee’s index were selected. Rats not meeting the obesity criteria were excluded from the study. Ultimately, a model of obese rats with IR was successfully established.

In the Obs group, the remaining rats were randomly divided into four subgroups: the model group, the PI3K/AKT inhibition group, the TLR/NF-κB inhibition group, and the combined PI3K/AKT + TLR/NF-κB inhibition group, with 40 rats in each subgroup. The animal models were constructed as shown in Table 1.

Table 1

Construction of animal models

Groups Number of rats Treatment for rats
Obs group Ctrl group 40 Normal rats fed with ordinary diet
Model group 40 Simple obese rats
PI3K/AKT inhibition group 40 Obesity rats with abnormal glucose metabolism + PI3K/AKT inhibitor LY294002 injected via tail vein
TLR/NF-κB inhibition group 40 Obesity rats with abnormal glucose metabolism + injection of TLR/NF-κB inhibitor BAY11-7082 via tail vein
PI3K/AKT + TLR/NF-κB inhibition group 40 Obesity rats with abnormal glucose metabolism + injections of BAY11-7082 and LY294002 via tail vein

2.3 Observation indicators

  1. General conditions, including body weight, anogenital distance, and 24-h food intake of the rats, were measured before the intervention (week 0) and at weeks 2, 4, 6, and 8 of the intervention. Lee’s index was then calculated.

  2. The IPGTT was conducted at week 6 of the intervention. Rats were fasted for 14 h prior to the test. Fasting blood glucose was first measured (recorded as 0 min). Subsequently, a 50% glucose solution was intraperitoneally injected based on the rats’ body weight, and blood glucose levels were assessed at 15-, 30-, 60-, and 120-min post-injection.

  3. The IPITT was also performed at week 6 of the intervention. Rats were fasted for 14 h before the test, and fasting insulin levels were first measured (0 min). Insulin was then intraperitoneally injected based on body weight, with insulin levels measured at 15-, 30-, 60-, and 120-min post-injection.

  4. Glucose infusion rate (GIR) was measured. At the end of the intervention, 10 rats from each group were randomly selected to undergo a high-insulin euglycemic clamp procedure to assess insulin sensitivity.

2.4 Weight determination of adipose tissue and skeletal muscle and HE staining

After serum samples were collected, the rats were euthanized, and white adipose tissue from the abdominal reproductive organs and perirenal fat was extracted from each group. The tissue was blotted dry with filter paper and weighed using an electronic balance with an accuracy of 0.1 mg. Each sample was weighed three times, and the average weight was recorded.

A small piece of white adipose tissue from the same abdominal location was taken from each group of rats, fixed in 2.5% paraformaldehyde in ethanol, and subjected to gradient alcohol dehydration before being embedded in paraffin. Sections were then stained with HE and examined for tissue morphology under a 400× optical microscope.

2.5 Western blot analysis

Western blotting was used to detect the expression of proteins related to the PI3K/AKT signaling pathway (including PI3K, phosphorylated PI3K [p-PI3K], AKT, and phosphorylated AKT [p-AKT]) and the TLR/NF-κB signaling pathway (including p-P65, TLR-4, and NF-κB).

First, adipose tissue from the rats was lysed on ice using pre-chilled RIPA lysis buffer, followed by centrifugation at 12,000 rpm for 15 min at 4°C. Protein concentrations were determined using the BCA method, and 10 μL from each sample was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS-PAGE gel was placed into the electrophoresis chamber, where an initial voltage of 80 V was set using an electrophoresis apparatus (Nippon Genetics, Germany). When the bromophenol blue marker reached the separating gel, the voltage was increased to 160 V. Upon completion of the electrophoresis, the stacking gel was removed, and the separating gel was assembled in the following order: sponge/filter paper/separating gel/polyvinylidene fluoride membrane/filter paper/sponge, and then placed into the transfer chamber. A wet transfer system (Bio-Rad Laboratories, Inc., USA) was utilized to transfer the proteins at 100 V for 60 to 120 min.

After transfer, the membrane was placed at 25°C and blocked with 5% non-fat milk for 2 h. The membrane was then washed three times for 10 min each with Tris-buffered saline with Tween (TBST). The primary antibody, specific to the target protein, was added, and the membrane was incubated overnight (approximately 24 h) at 4°C. Following this, the membrane was washed again three times for 10 min each with TBST. Subsequently, the secondary antibody, which targets the primary antibody, was added and incubated for 1 h at 25°C with shaking. After incubation, the secondary antibody was discarded, and the membrane was washed three times for 10 min each with TBST. Once washing was complete, the membrane was removed, blotted with filter paper to remove excess liquid, and placed in a darkroom. Chemiluminescence reagent (purchased from Beijing ZhiJie FangYuan Technology Co., Ltd.) was evenly applied to the membrane to ensure thorough exposure. Finally, the membrane was placed on a development board and detected using a gel imaging system, with grayscale values analyzed using the ImageJ image analysis system.

2.6 Statistical methods

Data analysis was performed using SPSS 23.0. Measurement data that followed a normal distribution are presented as mean ± standard deviation (x̄ ± s). Comparisons among multiple groups were conducted using a one-way analysis of variance, while comparisons between two groups were made using an independent samples t-test. Categorical data are expressed as percentages (%) and analyzed using the χ² test. All statistical tests were two-tailed, with P < 0.05 considered indicative of statistically significant differences.

3 Results

3.1 Establishment of obesity rat models

Body weight, anogenital distance, and 24-h food intake of the rats were measured before the intervention (week 0) and at weeks 2, 4, 6, and 8 of the intervention, with results shown in Figure 1. At baseline, there were no significant differences among the groups in terms of body weight, anogenital distance, or 24-h food intake (P > 0.05). However, after 6 and 8 weeks of intervention, the body weight of rats in the Obs group was significantly higher than that of the Ctrl group, with statistical significance (P < 0.05). The 24-h food intake of the Obs group remained consistently higher than that of the Ctrl group at weeks 2, 4, 6, and 8, also showing statistical significance (P < 0.05). Additionally, the Lee’s index in the Obs group was significantly higher than that in the Ctrl group (P < 0.05), although there was no significant difference in anogenital distance between the two groups (P > 0.05). These results indicated that the high-fat diet successfully induced obesity in the rat model, achieving the desired experimental outcomes.

Figure 1 Comparison of body weight, anus-nose length, and 24-h food intake between the Ctrl and Obs groups. (a) Body weight; (b) anus-nose length; (c) 24-h food intake; and (d) Lee’s index. Note: *P < 0.05 vs Ctrl group.
Figure 1

Comparison of body weight, anus-nose length, and 24-h food intake between the Ctrl and Obs groups. (a) Body weight; (b) anus-nose length; (c) 24-h food intake; and (d) Lee’s index. Note: *P < 0.05 vs Ctrl group.

3.2 Results of IPGTT and IPITT

The statistical results for blood glucose and insulin levels at 0, 15, 30, 60, and 120 min during the IPGTT and IPITT tests are shown in Figure 2. The IPGTT results indicated that 30 min after intraperitoneal injection of 50% glucose, both Obs and Ctrl groups reached peak blood glucose levels. However, blood glucose levels in the Obs group were significantly higher than those in the Ctrl group, with statistical significance (P < 0.05). The IPITT results demonstrated that serum insulin levels peaked at 15 min after intraperitoneal insulin injection in both groups, with insulin levels in the Obs group significantly higher than those in the Ctrl group, also showing statistical significance (P < 0.05).

Figure 2 Results of IPGTT and IPITT. (a) IPGTT and (b) IPITT. Note: *marked considerable differences compared to the results of the Ctrl group (P < 0.05).
Figure 2

Results of IPGTT and IPITT. (a) IPGTT and (b) IPITT. Note: *marked considerable differences compared to the results of the Ctrl group (P < 0.05).

3.3 Contrast of GIR

In the comparison of GIR, rats in the model group, the PI3K/AKT inhibition group, the TLR/NF-κB inhibition group, and the PI3K/AKT + TLR/NF-κB combined inhibition group exhibited significantly lower GIR compared to the Ctrl group (P < 0.05). This indicates a marked reduction in insulin sensitivity among the rats in these treatment groups. Notably, the GIR in the model group was significantly lower than that in the Ctrl group, further validating the successful establishment of the obese rat model. These results clearly demonstrate the impact of different interventions on insulin sensitivity (Figure 3).

Figure 3 Comparison of GIR. Note: *indicated differences were substantial versus Ctrl group (P < 0.05).
Figure 3

Comparison of GIR. Note: *indicated differences were substantial versus Ctrl group (P < 0.05).

3.4 Weight determination of adipose tissue and skeletal muscle

The results of the measurements for adipose tissue and skeletal muscle weight are shown in Figure 4. After 8 weeks of intervention, the abdominal fat weight and relative abdominal white fat weight in the Obs group were significantly higher than those in the Ctrl group, with statistical significance (P < 0.05). However, in the PI3K/AKT + TLR/NF-κB combined inhibition group, both abdominal fat weight and relative abdominal white fat weight were significantly lower compared to the model group, also showing statistical significance (P < 0.05).

Figure 4 Results of adipose tissue weight and skeletal muscle weight. (a) abdominal fat weight; (b) relative weight of abdominal white fat; (c) weight bilateral triceps of calf; and (d) relative weight of skeletal muscle. Note: *and # indicated considerable differences compared to Ctrl group and model group, respectively (P < 0.05).
Figure 4

Results of adipose tissue weight and skeletal muscle weight. (a) abdominal fat weight; (b) relative weight of abdominal white fat; (c) weight bilateral triceps of calf; and (d) relative weight of skeletal muscle. Note: *and # indicated considerable differences compared to Ctrl group and model group, respectively (P < 0.05).

Additionally, the relative skeletal muscle weight in all rats of the Obs group was significantly lower than that in the Ctrl group, with statistical significance (P < 0.05). Notably, the relative skeletal muscle weight in the PI3K/AKT inhibition group and the PI3K/AKT + TLR/NF-κB combined inhibition group was significantly higher than in the model group, also showing statistical significance (P < 0.05). However, there were no significant differences in the weight of the bilateral gastrocnemius muscles among the groups (P > 0.05). These results highlight the impact of different signaling pathway inhibitions on adipose tissue and skeletal muscle in rats.

3.5 HE staining of adipose tissue sections

Histological examination using HE staining revealed that the adipocytes in the Ctrl group rats were well-rounded, relatively small, uniform in size, and showed no signs of inflammatory cell infiltration. In contrast, the adipocytes in the Obs group rats were markedly enlarged, irregular in size, and appeared swollen. The fat droplets were enlarged, cell boundaries were indistinct, and there was evidence of cellular fusion (Figure 5). These HE staining results clearly demonstrate the impact of a high-fat diet on adipose tissue structure, further confirming the successful establishment of the obesity model.

Figure 5 Morphological observation results of adipose tissues (×40 times). (a) Ctrl group and (b) Obs group.
Figure 5

Morphological observation results of adipose tissues (×40 times). (a) Ctrl group and (b) Obs group.

3.6 Western blot analysis of related proteins in PI3K/AKT and TLR/NF-κB pathways

By analyzing the signaling pathway proteins in adipose tissue, the expression of proteins related to the PI3K/AKT (including PI3K, p-PI3K, AKT, and p-AKT) and TLR/NF-κB (including p-P65, TLR-4, and NF-κB) signaling pathways across the different groups is shown in Figure 6. There was no significant difference in PI3K protein expression between the model and Ctrl groups (P > 0.05), but the expression of p-PI3K was significantly lower in the Obs group compared to the Ctrl group (P < 0.05). No significant difference in AKT protein expression was observed between the model and Ctrl groups (P > 0.05), while p-AKT expression was significantly reduced in the Obs group (P < 0.05).

Figure 6 Expression levels of related proteins in PI3K/AKT and TLR/NF-κB pathways detected by Western blotting. (a) PI3K/AKT signaling-related protein levels; (b) PI3K/AKT signaling -related protein relative levels; (c) TLR/NF-κB signaling -related protein levels; and (d) TLR/NF-κB signaling-related protein relative levels. Note: *P < 0.05 vs Ctrl group.
Figure 6

Expression levels of related proteins in PI3K/AKT and TLR/NF-κB pathways detected by Western blotting. (a) PI3K/AKT signaling-related protein levels; (b) PI3K/AKT signaling -related protein relative levels; (c) TLR/NF-κB signaling -related protein levels; and (d) TLR/NF-κB signaling-related protein relative levels. Note: *P < 0.05 vs Ctrl group.

Regarding the TLR/NF-κB pathway, there were no significant differences in p-P65, TLR-4, and NF-κB protein expression between the model and Ctrl groups (P > 0.05). However, in the PI3K/AKT inhibition group and the PI3K/AKT + TLR/NF-κB combined inhibition group, the expression of these proteins was significantly lower than in the Ctrl group (P < 0.05). These results indicated that inhibition of the PI3K/AKT and TLR/NF-κB pathways significantly reduced the expression of related proteins, thereby affecting IR and inflammatory responses.

4 Discussion

Obesity is a condition characterized by abnormal distribution or excessive accumulation of fat in the body. Simple obesity, which accounts for approximately 95% of all obesity cases, refers to obesity without underlying endocrine disorders. Changes in dietary habits, particularly excess food intake, are the primary causes of obesity. The nutritional obesity rat model is one of the most used animal models for obesity research, due to its many similarities with human obesity induced by high-fat diets, and is extensively used in studies on obesity and anti-obesity medications [17,18]. This study used a high-fat diet to simulate human obesity factors and induce obesity in rats. Body mass index (BMI) is commonly used to measure obesity in humans, while Lee’s index is frequently used to assess obesity in rats [19]. In this experiment, rat body weight, snout-to-anal length, and 24-h food intake were measured before intervention (week 0) and at weeks 2, 4, 6, and 8 post-intervention. The results indicated that, after 6 and 8 weeks of intervention, the body weight of rats in the Obs group was significantly higher than that of the Ctrl group (P < 0.05). Additionally, the 24-h food intake in the Obs group was consistently higher than that in the Ctrl group at weeks 2, 4, 6, and 8 (P < 0.05), and Lee’s index was also significantly higher in the Obs group compared to the Ctrl group (P < 0.05). Schütte et al. investigated whether maternal diabetes during pregnancy, without accompanying obesity, negatively affects the metabolic health of male offspring [20]. The study used a rat model where maternal type 2 diabetes was induced by insulin receptor inhibition, and this condition was maintained during pregnancy. The metabolic health of male offspring was then assessed. The study found that the weight gain and blood glucose levels of male offspring during puberty and adulthood were similar to those of the Ctrl group. After a high-fat diet, there were no significant differences in weight, fat mass, glucose, or insulin tolerance tests. This suggests that, in this model, isolated maternal hyperglycemia and hyperinsulinemia (without obesity) did not significantly impact the metabolic health of the offspring. It was hypothesized that other maternal metabolic parameters, such as obesity, may play a more crucial role in fetal metabolic programming. Compared to our study, both studies utilized rat models to investigate metabolic health and focused on the impact of high-fat diets on rats, with both involving long-term observations of body weight and metabolic parameters such as glucose tolerance.

The impact of carbohydrates on glucose metabolism remains controversial. Data indicate that increasing the proportion of high-carbohydrate foods can lead to higher energy intake and increased metabolic load on insulin secretion, which may adversely affect obese individuals. However, recent studies have highlighted that the type of carbohydrates consumed is closely related to glucose metabolism [21,22,23]. The high-insulin euglycemic clamp technique operates by continuously infusing a fixed amount of insulin or adjusting GIRs to disrupt the body’s endogenous glucose-insulin feedback mechanism, thereby maintaining blood glucose at baseline levels while keeping plasma levels of exogenous insulin relatively high. When GIR and metabolic rate stabilize at equilibrium, GIR represents the rate of glucose uptake by tissues such as muscle, fat, and liver. Thus, GIR serves as a sensitive indicator of insulin action on peripheral tissues. A higher GIR reflects greater insulin sensitivity. In this study, intraperitoneal glucose and insulin injections were used to mimic poor dietary habits in humans. Results showed that blood glucose and insulin levels in the Obs group were significantly higher (P < 0.05), while their GIR was markedly lower than that of the Ctrl group (P < 0.05). These findings are consistent with those of Crites et al. [24], indicating decreased insulin sensitivity, impaired insulin function, and IR in obese rats.

PI3K activates AKT and catalyzes its phosphorylation, which implies that when the PI3K/AKT signaling pathway is activated, the proportion of p-AKT increases. Conversely, when the PI3K/AKT signaling pathway is inhibited, the expression of p-AKT decreases. The results indicated that the expression levels of p-PI3K and p-AKT were significantly reduced in both the PI3K/AKT inhibition group and the PI3K/AKT + TLR/NF-κB combined inhibition group (P < 0.05), suggesting that the activity of the PI3K/AKT signaling pathway was suppressed in these groups. After the successful establishment of the obesity rat model, the relevant indicators of the signaling pathways in the rats’ adipose tissue were further examined. This study experimentally verified the direct association between changes in the activity of the PI3K/AKT signaling pathway and the expression of its downstream protein, p-AKT. The results demonstrated that inhibition of the PI3K/AKT pathway significantly reduced the phosphorylation levels of related proteins, further highlighting the pathway’s crucial role in metabolic regulation and the pathology of obesity. By assessing the indicators of these pathways in an obesity model, we can gain deeper insights into the relationship between obesity and signaling pathway dysregulation. The primary function of the PI3K/AKT signaling pathway in adipocytes is regulating insulin signaling, promoting glucose uptake, and facilitating lipogenesis. In the obesity model, a high-fat diet typically induces IR, leading to decreased activity of the PI3K/AKT pathway. Consequently, impaired insulin signaling in adipocytes may manifest as reduced glucose uptake and increased fat accumulation, aligning with the characteristics of IR. Additionally, the significant reduction in the expression levels of p-PI3K and p-AKT proteins indicates pathway suppression. The TLR/NF-κB signaling pathway primarily participates in immune and inflammatory responses, with TLR-4 capable of recognizing molecules such as saturated fatty acids, activating downstream NF-κB, and promoting the release of inflammatory factors like TNF-α and IL-6. In the obesity model, a high-fat diet can induce chronic low-grade inflammation by activating the TLR-4/NF-κB pathway, representing a crucial mechanism behind metabolic disorders associated with obesity. Consequently, in the TLR/NF-κB inhibition group, the inflammatory response in adipocytes was significantly suppressed, with reduced expression levels of TLR-4 and NF-κB-related proteins, thereby decreasing the production of inflammatory factors, which may help alleviate obesity-related chronic inflammation. The PI3K/AKT + TLR/NF-κB combined inhibition group simultaneously inhibited both insulin signaling and inflammatory pathways, theoretically allowing for more pronounced metabolic disturbances. The inhibition of the PI3K/AKT pathway may exacerbate IR, while TLR/NF-κB pathway inhibition reduces the inflammatory response. As a result, the expression levels of p-PI3K, p-AKT, TLR-4, and NF-κB were significantly diminished in the combined inhibition group. Adipocytes displayed impaired insulin signaling alongside a lower inflammatory response, suggesting that this group’s experiments may elucidate the complex balance between metabolic dysregulation and inflammation under the joint action of these two pathways.

Ghaiad et al. investigated the effects of the thiamine derivative, alpha-lipoic acid (Sulbutiamine), on streptozotocin-induced diabetic nephropathy [25]. The study assessed the impact of alpha-lipoic acid on renal function and related signaling pathways by successfully inducing a diabetic nephropathy model in rats. The results indicated that alpha-lipoic acid treatment reduced fasting blood glucose levels and improved renal function in diabetic rats. Furthermore, alpha-lipoic acid significantly decreased the levels of TLR-4, NF-κB, MDA, and PKC and suppressed the production of pro-inflammatory cytokines TNF-α and IL-1β, as well as the levels of TGF-β1. The study also demonstrated that alpha-lipoic acid alleviated tissue pathological changes associated with DN, indicating its renal protective effects through antioxidant, anti-inflammatory, and anti-fibrotic mechanisms. In comparison to this study, both research efforts found that specific interventions could inhibit the activity of the TLR-4/NF-κB signaling pathway. The mentioned study suggested that alpha-lipoic acid reduces the expression of TLR-4 and NF-κB, thereby exerting anti-inflammatory effects. Conversely, our study showed that the PI3K/AKT inhibition group and the combined PI3K/AKT + TLR/NF-κB inhibition group significantly suppressed the activity of the PI3K/AKT signaling pathway and inhibited the activation of the TLR-4/NF-κB pathway. Both studies highlight the role of intervention measures in reducing inflammation, demonstrating that modulation of the TLR-4/NF-κB and other related signaling pathways can play a crucial anti-inflammatory and protective role in metabolic disorders associated with diabetes or obesity.

5 Conclusion

This study successfully established an obesity rat model and analyzed the expression of the PI3K/AKT and TLR/NF-κB signaling pathways using methods such as IPGTT, IPITT, HE staining, and Western blotting. The results indicated that a high-fat diet activated the PI3K/AKT and TLR-4/NF-κB signaling pathways in adipocytes. This activation appears to be mediated by the regulation of protein levels, including PI3K, p-PI3K, AKT, p-AKT, p-P65, TLR-4, and NF-κB. A limitation of this study is that it assessed changes in body composition only through the relative weights of abdominal fat and skeletal muscle, lacking a more precise analysis of body composition. Future research should include detailed body composition analyses, contingent upon available resources and time. These findings provide a theoretical basis for further exploring the mechanisms underlying obesity-related metabolic diseases and may offer insights for the development of future research or clinical intervention strategies.

  1. Funding information: Authors state no funding involved.

  2. Author contributions: Liya Song was responsible for experimental design and overall research strategy and led the implementation of experiments related to the PI3K/AKT and TLR/NF-κB signaling pathways. Liya Song also conducted data analysis, interpreted experimental results, and wrote the initial draft of the manuscript. Lihua Li was in charge of constructing the obesity rat model and performing Western blot experiments related to the signaling pathways. She also contributed to data collection and statistical analysis, providing critical theoretical support and literature review for the manuscript. Liya Song and Lihua Li jointly discussed and revised the final manuscript to ensure its scientific accuracy and completeness. All authors reviewed the manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2024-05-28
Revised: 2024-10-21
Accepted: 2024-11-14
Published Online: 2024-12-31

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
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https://doi.org/10.1515/biol-2022-1014
Keywords for this article
obesity rat model; high-fat diet; phosphatidylinositol-3-kinase/protein kinase B; Toll-like receptor/nuclear factor kappa B; differences; expression
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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