Lower body adipose tissue removal decreases glucose tolerance and insulin sensitivity in mice with exposure to high fat diet.

It has been postulated that the protective effects of lower body subcutaneous adipose tissue (LBSAT) occur via its ability to sequester surplus lipid and thus serve as a "metabolic sink." However, the mechanisms that mediate this protective function are unknown thus this study addresses this postulate. Ad libitum, chow-fed mice underwent Sham-surgery or LBSAT removal (IngX, inguinal depot removal) and were subsequently provided chow (Chow; typical adipocyte expansion) or high fat diet (HFD; enhanced adipocyte expansion) for 5 weeks. Primary outcome measures included glucose tolerance and subsequent insulin response, muscle insulin sensitivity, liver and muscle triglycerides, adipose tissue gene expression, and circulating lipids and adipokines. In a follow up study the consequences of extended experiment length post-surgery (13 wks) or pre-existing glucose intolerance were examined. At 5 wks post-surgery IngX in HFD-fed mice reduced glucose tolerance and muscle insulin sensitivity and increased circulating insulin compared with HFD Sham. In Chow-fed mice, muscle insulin sensitivity was the only measurement reduced following IngX. At 13 wks circulating insulin concentration of HFD IngX mice continued to be higher than HFD Sham. Surgery did not induce changes in mice with pre-existing glucose intolerance. IngX also increased muscle, but not liver, triglyceride concentration in Chow- and HFD-fed mice 5 wks post-surgery, but chow group only at 13 wks. These data suggest that the presence of LBSAT protects against triglyceride accumulation in the muscle and HFD-induced glucose intolerance and muscle insulin resistance. These data suggest that lower body subcutaneous adipose tissue can function as a "metabolic sink."