Volume 33, Issue 1 - SPECIAL ISSUE: ‘SUBCUTANEOUS AND VISCERAL ADIPOSE TISSUES: ALLIES OR ENEMIES?’ / Editors: Gérard S. Chetrite and Bruno Fève

Metabolic and cardiovascular diseases are increasing worldwide due to the rise in the obesity epidemic. The metabolic consequences of obesity vary by distribution of adipose tissue. Visceral and ectopic adipose accumulation are associated with adverse cardiometabolic consequences, while gluteal-femoral adipose accumulation are negatively associated with these adverse complications and subcutaneous abdominal adipose accumulation is more neutral in its associations. Gender, race and ethnic differences in adipose tissue distribution have been described and could account for the observed differences in risk for cardiometabolic disease. The mechanisms behind the differential impact of adipose tissue on cardiometabolic risk have started to be unraveled and include differences in adipocyte biology, inflammatory profile, connection to systemic circulation and most importantly the inability of the subcutaneous adipose tissue to expand in response to positive energy balance.

Background Severe mental illnesses (SMIs), i.e. major depression, schizophrenia and bipolar disorder, are associated with an elevated risk for the development of type-2 diabetes mellitus and cardiovascular disorders. Several factors have been associated with increased cardiometabolic morbidity and mortality in SMI, including lifestyle factors (smoking, inactivity, unhealthy diet), endocrine and immunologic alterations; however, the underlying mechanisms remain to be fully uncovered. It is now well accepted that visceral adipose tissue (VAT) promotes the development of cardiometabolic disorders, at least in part by inflammatory and metabolic functions. Methods This paper reviews studies concerning VAT, with special focus on intra-abdominal and pericardial adipose tissue, in SMI. Results In patients with SMI, several studies have been performed concerning VAT. Most of these studies reported alterations of VAT particularly in patients with major depression and schizophrenia, independent of body weight and body mass index. Some of the studies also reported an increased cardiometabolic risk. Conclusion Patients with SMI are at increased risk of developing cardiometabolic disorders, and display increased amounts of VAT. As studies so far were mainly performed on patients before the onset of cardiometabolic disorders, VAT may serve as a biomarker for patients with SMI to assess cardiometabolic risks beyond established risk scores. Further, interventions aiming at reducing VAT in SMI are highly recommended in long-term multimodal treatment plans.

Metabolic syndrome (MetS) is a common global problem that comprises the cardio-metabolic cluster and predisposes to both diabetes and cardiovascular diseases. Although the pathogenic mechanisms have not been elucidated, both increased inflammation and insulin resistance play a pivotal role. It appears that both monocyte/macrophages and adipose tissue (AT) conspire to accentuate both the pro-inflammatory state and increased insulin resistance. Whilst there are scant data on visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) biology, there are data on subcutaneous adipose tissue (SAT) dysregulation. There is a significant increase in macrophages and crown-like structures in the SAT of patients with MetS. With respect to adipokines, there is an increase in plasma leptin, plasminogen activator inhibitor-1, retinol-binding protein-4 (RBP-4), chemerin, serum amyloid-A, C-reactive protein (CRP), interleukin-1, -6, -8, lipopolysaccharide, fetuin A (FetA) and a decrease in adiponectin and omentin-1. All of the abnormalities in plasma were also confirmed for SAT-secreted adipokines except for adiponectin and RBP-4 which derive largely from VAT. As many of these biomediators correlate with both insulin resistance and increased inflammation, we can posit that dysregulation of SAT is detrimental and contributes to both the pathogenesis of MetS and its sequalae. Furthermore, as future directions, much work is needed with respect to VAT/EAT biology, autophagy, sirtuins, the gut microbiome, browning of AT, to further elucidate this common syndrome and identify potential therapeutic targets to forestall its serious complications.

Adipose tissue exists in many locations or depots that differ from one another based on numerous and various characteristics. The unique “layered” anatomical feature of subcutaneous adipose tissue (SAT) in man and the pig is reviewed and discussed. The origin of fetal pig adipose tissue subcutaneous layers is reviewed before the onset of adipogenesis and after the overt adipogenesis. Furthermore, the distinguishing characteristics of developing outer SAT layer (OSQ) and middle SAT layer (MSQ) in pigs are reviewed. These characteristics include adipocyte hypertrophy, metabolism and genetic regulation. The MSQ layer is the major layer in the pig and expands to the greatest degree in obesity and growth. Abdominal SAT in man is composed of deep SAT (dSAT) and superficial SAT (sSAT) layers. Clearly, dSAT expands disproportionally more than sSAT with increasing obesity in Caucasian males which precipitates a number of human pathologies associated with increased adiposity. We reviewed the considerable evidence that demonstrates the distinction between sSAT and dSAT which includes higher levels of saturated fatty acids (FAs) and greater levels of lipolysis in dSAT. Furthermore, dSAT expresses more metabolic and inflammatory genes. Studies comparing visceral adipose tissue (VAT) and dSAT indicate that both depots are implicated in insulin resistance (IR) and other human pathologies. Epigenetic studies of MSQ and dSAT have begun to indicate a role for DNA methylation in gene regulation of these depots. Further studies of dSAT and MSQ are warranted as they are clearly a major manifestation of obesity.

Background Lipedema is a chronic disorder presenting in women during puberty or other times of hormonal change such as childbirth or menopause, characterized by symmetric enlargement of nodular, painful subcutaneous adipose tissue (fat) in the limbs, sparing the hands, feet and trunk. Healthcare providers underdiagnose or misdiagnose lipedema as obesity or lymphedema. Materials and methods The benefits (friend) and negative aspects (foe) of lipedema were collected from published literature, discussions with women with lipedema, and institutional review board approved evaluation of medical charts of 46 women with lipedema. Results Lipedema is a foe because lifestyle change does not reduce lipedema fat, the fat is painful, can become obese, causes gait and joint abnormalities, fatigue, lymphedema and psychosocial distress. Hypermobility associated with lipedema can exacerbate joint disease and aortic disease. In contrast, lipedema fat can be a friend as it is associated with relative reductions in obesity-related metabolic dysfunction. In new data collected, lipedema was associated with a low risk of diabetes (2%), dyslipidemia (11.7%) and hypertension (13%) despite an obese average body mass index (BMI) of 35.3 ± 1.7 kg/m 2 . Conclusion Lipedema is a painful psychologically distressing fat disorder, more foe than friend especially due to associated obesity and lymphedema. More controlled studies are needed to study the mechanisms and treatments for lipedema.