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1 Department of Foods and Nutrition and Department of Biology, University of Georgia, Athens, Georgia, USA
* To whom correspondence should be addressed. E-mail: harrisrb{at}uga.edu.
Mice adapted to a high-fat diet are reported to be leptin resistant but we previously reported that mice fed a high-fat (HF) diet and housed at 23° C remained sensitive to peripheral leptin and specifically lost body fat. This study tested whether leptin action was impaired by a combination of elevated environmental temperature combined and a HF diet. Male C57BL/6 mice were adapted to low-fat (LF) or HF diet from 10 days of age and were housed at 27° C from 28 days of age. From 35 days of age baseline food intake and body weight were recorded for one week and then mice on each diet were infused with 10 ug leptin/day or PBS from an intraperitoneal miniosmotic pump for 13 days. HF-fed mice had a higher energy intake than LF-fed mice and were heavier, but not fatter. Serum leptin was lower in PBS-infused HF- than LF-fed mice. Leptin significantly inhibited energy intake of both LF-fed and HF-fed mice and this was associated with a significant increase in hypothalamic long-form leptin receptors with no change in short-form leptin receptor or brown fat uncoupling protein-1 mRNA expression. Leptin significantly inhibited weight gain in both LF- and HF-fed mice but reduced the percent body fat mass only in LF-fed mice. Percent lean and fat tissue in HF-fed mice did not change, implying that overall growth had been inhibited. These results suggest that dietary fat modifies the mechanisms responsible for leptin-induced changes in body fat content and that those in HF-fed mice are sensitive to environmental temperature.
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