Publications

Abstract

Adipose tissue distribution is a major determinant of human mortality and morbidity. In mice, intra-abdominal transplantation of subcutaneous adipose tissue protects against glucose intolerance and insulin resistance, but the underlying mechanisms are not well understood. Here, we investigate changes in systemic inflammation, adipokines and tissue-specific glucose uptake in male mice implanted intra-abdominally with either inguinal (subcutaneous) or epididymal (visceral) adipose tissue and fed a high-fat diet for up to 17 weeks. Glucose tolerance was 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. High-fat diet-induced increases in systemic pro-inflammatory cytokines were also markedly suppressed, some from as early as 4 weeks post-transplant. Specifically, early differences in plasma concentrations of tumor necrosis factor-alpha and interleukin-17 concentrations predicted subsequent improvements in glucose tolerance and insulinaemia. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, a marked induction of skeletal muscle gene expression. Consistent with their improved glucose tolerance, mice receiving subcutaneous fat displayed a significant attenuation of high-fat diet-induced hepatic triglyceride accumulation. These findings have implications for our future understanding of the relationship between regional adiposity and metabolic disease.