Oral Presentation Australian & New Zealand Obesity Society 2014 Annual Scientific Meeting

Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice (#25)

Samantha L. Hocking 1 2 , Rebecca L. Stewart 1 , Amanda E. Brandon 1 , Eurwin Suryana 1 , Emily M. Baldwin 1 , Ganesh A. Kolumam 3 , Michael Medynskyj 4 5 , Sinead P. Blaber 4 5 , Elisabeth Karsten 4 5 , Benjamin R. Herbert 4 5 , Gregory J. Cooney 1 6 , Michael M. Swarbrick 1 7
  1. Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. Endocrinology, Royal North Shore Hospital, St. Leonard's, NSW, Australia
  3. Tumor Biology and Angiogenesis, Genentech, Inc, South San Francisco, California, United States of America
  4. Regeneus, Ltd, Pymble, NSW, Australia
  5. Dept. of Chemistry and Biomolecular Science, Macquarie University, Sydney, NSW, Australia
  6. St Vincent's Clinical School, University of New South Wales Australia, Darlinghurst, NSW, Australia
  7. School of Medical Sciences, University of New South Wales, Kengington, NSW, Australia

Background: Adipose tissue distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous adipose tissue protects against glucose intolerance and insulin resistance, but the underlying mechanisms are not well understood. 

Methods: We investigated changes in adipokines, tissue-specific glucose uptake and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal (subcutaneous) or epididymal (visceral) adipose tissue and fed a high-fat diet (HFD) for up to 17 weeks. Gene expression in grafted and endogenous adipose tissues was examined by microarray, and the expression of 84 fatty liver-associated genes involved were measured using PCR arrays (Qiagen). Plasma cytokine concentrations were measured using Bio-plex Pro assays (Bio-Rad). 

Results: Glucose tolerance was significantly improved in mice receiving subcutaneous adipose tissue from 6 weeks after transplantation, and was observed independently of body weight, skeletal muscle glucose uptake, and plasma leptin and adiponectin concentrations. In these mice, high-fat diet-induced increases in plasma concentrations of several pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-12p70, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) were markedly suppressed, relative to sham-operated mice. Notably, plasma concentrations of IL-17 and MIP-1β were reduced from as early as 4 weeks after transplantation. Of these cytokines, differences in plasma TNF-α and IL-17 concentrations significantly predicted subsequent improvements in glucose tolerance and insulinaemia in the entire group of mice (n=40). 

Grafted fat displayed a significant increase in glucose uptake and unexpectedly, a marked induction of skeletal muscle gene expression. Consistent with improved glucose tolerance, hepatic triglyceride accumulation was significantly attenuated in mice receiving subcutaneous fat transplants. In contrast, mice receiving additional intra-abdominal adipose tissue displayed the greatest degree of hepatic triglyceride accumulation, and uniquely elevated plasma IL-6 concentrations.

Conclusions: Intra-abdominal transplantation of subcutaneous fat has reproducible beneficial effects on glucose tolerance and systemic inflammation. Future studies will be required to identify the cell type(s) responsible for these effects, and potential sites for therapeutic intervention.