(11-07-15) Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice

Samantha L. Hocking, 
Rebecca L. Stewart, 
Amanda E. Brandon, 
Eurwin Suryana, 
Ella Stuart, 
Emily M. Baldwin, 
Ganesh A. Kolumam, 
Zora Modrusan,
Jagath R. Junutula, 
Jenny E. Gunton, 
…
Abstract
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-á, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1â [ÌIP-1â]), compared with sham-operated mice. Plasma IL-17 and MIP-1â concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-á 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.


SOURCE:
Diabetologia
July 2015, Volume 58, Issue 7, pp 1587-1600
Date: 22 Apr 2015

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