Reductions in adipose tissue mitochondrial content in high fat diet‐induced obesity and lean models of insulin resistance

Abstract

Insulin resistance is associated with reductions in adipose tissue mitochondrial content. It is not known how rapidly these changes occur and how they relate to changes in glucose homeostasis. In order to establish the temporal relationship between diet‐induced adipose tissue insulin resistance and mitochondrial content, rats were fed a high fat (HF) diet for 2, 4, or 6 weeks. We found that 6 weeks of HF feeding was necessary for reductions in mitochondrial content in epididymal adipose tissue to occur, as demonstrated by decreases in the protein content of cytochrome C and COXIV, reduced Mitotracker staining, and reductions in mitochondrial size as estimated by electron microscopy. Similar results were seen in dexamethasone treated rats, a model of lean insulin resistance. Intraperitoneal Glucose Tolerance Tests (IPGTT) were completed at 4 and 6 weeks to determine whole‐body insulin action. At 4 weeks and 6 weeks, the integrated AUC for glucose and insulin was higher in the HF fed rats versus control. Although reductions in mitochondrial content did not appear to precede changes in whole‐body insulin action, it did appear to be associated with a worsening of insulin sensitivity, a phenomenon that can occur in both lean and obese models of insulin resistance.Funding: Alberta Heritage Foundation for Medical Research, Natural Sciences and Engineering Research Council, Alberta Diabetes Institute