The combination of a high-fat diet and chronic stress aggravates insulin resistance in Wistar male rats.

We observed the effects of the combination of a high-fat diet and chronic stress on insulin resistance. Male Wistar rats were fed on either a control or a high-fat diet and given chronic stress with the electric foot shock or not for 10 weeks. After checking the glucose infusion rate (GIR) and the HOMA-IR index, the results showed that the three groups all revealed insulin resistance with increased free fatty acid (FFA), adrenocorticotropic hormone (ACTH) and corticosterone in the serum, in addition to increased tumour necrosis factor alpha (TNF-alpha) in the serum and adipose tissue, and decreased density of high affinity receptors (R1) and expression of peroxisome proliferator-activated receptor-alpha (PPARalpha) mRNA in the hepatocytes as compared with the control, but the highest alteration on aforementioned parameters revealed in the chronic stress fed with a high-fat diet. Significant interactions between high-fat diet and chronic stress were revealed on GIR, HOMA-IR index, FFA, ACTH, corticosterone, TNF-alpha (in adipose tissue) and R1. These observations strongly suggest that a combination of a high-fat diet and chronic stress can produce a synergic effect on aggravating insulin resistance associated with the abnormal hypothalamic-pituitary-adrenocortical axis, endocrine abnormality of the adipose tissue, and pathological changes of the liver.