Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Location, location, location:how fat distribution influences metabolic disease (#96)

Michael Swarbrick 1 2
  1. Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. School of Medical Sciences, University of New South Wales, Kengington, NSW, Australia

Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in humans. In particular, accumulation of intra-abdominal or ‘visceral’ AT (VAT) is associated with a greater incidence of insulin resistance (IR), type 2 diabetes and dyslipidaemia. This has been hypothesised to be due to increased free fatty acid (FFA) flux from VAT to the liver via the portal vein, alterations in AT secreted products (‘adipokines’), as well as local inflammation in AT.

Independently of VAT, increasing amounts of subcutaneous AT (SAT), particularly in the lower body, are associated with protection against glucose intolerance, IR, dyslipidaemia and atherosclerosis. Deficiency of SAT (lipodystrophy) is associated with severe IR. Functionally, lower-body SAT acts as a ‘metabolic sink’, protecting non-adipose tissues from excessive FFA exposure. Lower-body SAT also has a distinct developmental profile that may curtail pro-inflammatory and hypometabolic gene expression changes in obesity.

We have investigated the relationship between regional adiposity and metabolism by performing syngeneic AT transplantation in mice. Mice were implanted with either inguinal (subcutaneous) or epididymal (visceral) AT into the abdomen (subQ→vis or vis→vis, respectively) and fed a high-fat diet (HFD) for up to 17 weeks. From as early as 4 weeks after transplantation, subQ→vis transplantation markedly suppressed HFD-induced increases in plasma concentrations of many pro-inflammatory cytokines, including TNF-α, IL-6, IL-17, MCP-1, and MIP-1β. These cytokines predicted subsequent glucose tolerance and insulinaemia, which were sustainably improved in subQ→vis mice from 6 weeks post-transplantation. Relative to vis→vis mice, improved glucose tolerance in subQ→vis mice was accompanied by reduced hepatic triglyceride content and increased STAT3 expression. AT transplantation did not significantly affect body weight, skeletal muscle glucose uptake, or plasma leptin and adiponectin concentrations. The beneficial effects of subQ→vis transplantation on inflammation and glucose homeostasis have important implications for our understanding of the relationship between regional adiposity and metabolic disease.