Subcutaneous fat transplantation alleviates diet-induced glucose intolerance, systemic inflammation and hepatic fat accumulation in mice

SL Hocking1,2, RL Stewart1, AE Brandon1, E Suryana1, E Stuart1, JE Gunton3,4, BR Herbert5, DE James6, GJ Cooney1 and MM Swarbrick1,4

  1. Garvan Institute for Medical Research, Darlinghurst, Sydney NSW 2010
  2. Department of Endocrinology, Royal North Shore Hospital, Sydney NSW
  3. Westmead Clinical School, University of Sydney, Westmead NSW
  4. The Westmead Institute, The University of Sydney, Westmead NSW
  5. Dept. of Chemistry and Biomolecular Science, Macquarie University, Sydney NSW
  6. Charles Perkins Centre, The University of Sydney

Aims/hypothesis: Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood.
Methods: We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks.
Results: Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [MIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n=40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations.
Conclusions/interpretation: Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice. Our findings add to the emerging view that subcutaneous adipose tissue exerts considerable influence on hepatic glucose and lipid metabolism.