SAT-IMG · ABDOMINAL SUBCUTANEOUS ADIPOSE TISSUE DEPOTS AND HUMAN METABOLIC PROFILE: A NOVEL CONCEPT OF METABOLIC DYSFUNCTION IN ABDOMINAL OBESITY

ABDOMINAL SUBCUTANEOUS ADIPOSE TISSUE DEPOTS AND HUMAN METABOLIC PROFILE: A NOVEL CONCEPT OF METABOLIC DYSFUNCTION IN ABDOMINAL OBESITY

Background: Fat distribution is an important variable explaining metabolic heterogeneity of obesity. Abdominal subcutaneous adipose tissue (SAT) is divided by an anatomical structure called “Scarpa’s fascia” into a deep (dSAT) and superficial (sSAT) layer. The biological importance of these SAT layers is unclear, while there is no established method to quantify their expansion non-invasively in humans. Study objectives: a) To develop a new index of abdominal adiposity, based on non-invasive imaging, and determination of anatomical features of SAT layers b) To explore the biological differences between deep and superficial SAT in individuals within a wide range from normal weight to obesity. c) To explore the biological changes and the expansion of the SAT layers in menopause Study methodology: 830 participants have been enrolled consecutively from a random and population-based screening project of residents in Oxfordshire, the Oxford Biobank (www.oxfordbiobank.org.uk). Measurements of the Subcutaneous Adipose tissue layers and its two subdivisions (dSAT and sSAT) were performed using ultrasound. 800 of these subjects also underwent additional quantification of the fat in their body using a method called DEXA scanning. Biochemical samples were also taken for assessing cardiometabolic parameters such as, Cholesterol, Triglycerides, Glucose, Insulin-like Growth Factor Binding Protein 1. In order to develop further indices of obesity using ultrasound, we then quantified the depth of the fat in the thigh and in the deep abdomen (visceral fat) in this cohort. In order to explore the biological differences between deep and superficial SAT, ultra sound guided biopsies were performed in 43 of the cohort patients. Adipose tissue samples were taken with a technique that we have developed as part of the project. Samples were accessed for gene expression studies, fatty acid composition measurements and histology -adipocytes sizing. Main findings Male adiposity was characterized by a disproportionate expansion of dSAT which was strongly correlated with visceral adipose tissue mass by DEXA. dSAT depth was a strong predictor of global insulin resistance (HOMA-IR), liver-specific insulin resistance (Insulin-like growth factor binding protein 1) and Framingham Risk Score (which predicts the 10-year risk of these individuals for cardiovascular events) independently of other measures of adiposity in men. Moreover, dSAT had higher expression of proinflammatory, lipogenic and lipolytic genes and contained higher proportions of saturated FAs. There was increased proportion of small adipocytes in dSAT. To examine the role of menopause on the expansion of the two SAT layers, I performed ultrasound and magnetic resonance imaging (RRI) quantification of SAT in the female population of the study and compared the values between pre and post menopausal women. Menopause had no effect on the expansion of SAT or the distribution of its two layers sSAT and dSAT. Conclusions: Collectively it is underpinned by clear functional differences between the two distinct fat layers in the abdominal wall that dSAT is the part of SAT that matters for the relationship to obesity-related complications, at least in men and may have a different role than sSAT in the pathophysiology of male pattern adiposity and subsequent risk of diabetes and cardiovascular disease. Future studies are needed to elucidate the exact biological role of dSAT in human adiposity, and to clarify its potential value as a therapeutic target for the prevention of the cardiovascular complications of obesity.

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