THE EFFECTS OF A HIGH-FAT DIET ON LEPTIN MESSENGER-RNA, SERUM LEPTIN AND THE RESPONSE TO LEPTIN ARE NOT ALTERED IN A RAT STRAIN SUSCEPTIBLETO HIGH-FAT DIET-INDUCED OBESITY

Osborne-Mendel (OM) and S5B/PI rats differ in their sensitivity to dev elop obesity when fed a high fat (HF) diet; OM rats become obese, wher eas S5B/PI rats remain thin. We have investigated the possibilities th at either an impaired leptin response or resistance to leptin action u nderlies the sensitivity to this form of obesity in OM rats. In Experi ment 1, OM and S5B/PI rats fed a nonpurified diet were killed at d 0 o r were fed either a HF (56% fat energy) or a low fat (LF, 10% fat ener gy) diet for 2 or 7 d. The HF diet increased serum leptin significantl y by d 2 to levels that were similar in both rat strains. At 7 d, lept in levels were lower than at d 2 but remained higher than levels in th e d 0 control groups. The leptin mRNA:18S RNA ratio in epididymal adip ose tissue increased to higher levels in HF-fed OM rats than in S5B/PI rats fed that diet. However, although the LF diet had no effect in S5 B/PI rats, it increased leptin mRNA levels in epididymal adipose tissu e of OM rats compared with the controls fed the nonpurified diet. In E xperiment 2, OM and S5B/PI rats were fed HF or LF diets for 5 wk. At t hat time, their feeding response to a range of leptin doses (0, 1, 5 o r 10 mu g) given intracerebroventricularly was tested after overnight food deprivation. There was a similar dose-dependent reduction in ener gy intake in response to leptin in both OM and S5B/PI rats. These resp onses were independent of the diet. The data suggest that the suscepti bility of OM rats to HF diet-induced obesity is not related to either a loss of central sensitivity to leptin or a failure to enhance leptin production acutely, although the failure to maintain chronically incr eased levels of serum leptin could contribute to the obesity.