Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor

OBJECTIVE: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity METHODS: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection. RESULTS: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance. CONCLUSIONS: The contrasting effects of diet and photoperiod were consistent with the predictions of the ‘lipotoxicity hypothesis’. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.