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

Abdominal obesity is related to a number of adverse health outcomes but the relationships between expansion of certain fat depots and health outcomes, or the mechanisms by which adipose tissue communicates to the rest of the body, are unclear. Abdominal subcutaneous adipose tissue (SAT) is divided into two anatomically and morphologically distinct layers (above and below the Scarpa’s fascia). Preliminary data show that expansion of the deep SAT (dSAT) is strongly related to insulin resistance in a manner nearly identical to that of visceral adipose tissue, while superficial SAT (sSAT) appears to follow the pattern of lower body fat.I will use a range of techniques to characterize morphological and physiological differences between dSAT and sSAT in humans and also explore the potential for genetic regulation of fat layer distribution.I will establish a cohort of 1,000 subjects from Oxford Biobank, in whom the SAT layers will be quantified by ultrasound. The technique will be verified against magnetic resonance imaging. I will interrogate morphological/functional differences between SAT layers by taking ultrasound-guided biopsies. Functional characterization of the tissue will consist of transcriptomic patterns, analysis of tissue the explant secretome and adipocyte differentiation capacity. The host group has recently taken part in the first genome-wide association study searching for genetic variants associated with fat distribution and I will capitalize on this by using the unique SAT layer phenotype (n=1000) in combination with a new SNPchip (Illumina iSELECT to be employed in Oxford Biobank, n=5,000). The new SNPchip is based on largely functional variants derived from the 1,000-genomes project and exome sequences of 11,500 people.This study has the potential to provide the medical community with a new, easy-to-use anthropometric tool with strong relationships to obesity-related health outcomes together with functional annotations of the relevant tissues.