Endocrine Abstracts

Background: Rats on a free-choice (fc) diet of saturated fat and liquid sugar in addition to chow (fcHFHS) overeat persistently, and show increased hypothalamic neuropeptide Y and decreased melanocortin signaling, which reflects a hunger state despite hyperphagia. This response is specific for a fcHFHS diet, because when given the choice between fat and chow (fcHF) or between liquid sugar and chow (fcHS) hyperphagia is not observed. Because leptin signaling is important for the regulation of feeding behavior, we determined whether rats on a fcHFHS diet become leptin resistant, and whether this depends on the free-choice component.

Methods: Rats were subjected to a chow, fcHF, fcHS or fcHFHS diet. After either i.p. or i.c.v. injections of leptin or vehicle food intake was determined. Another group was subjected to chow, fcHFHS or a non-choice HFHS (ncHFHS) diet and the extent of leptin resistance was determined by i.p. injections of leptin or vehicle. The ncHFHS diet consisted of pellets containing the same ingredients and the same percentages for fat, sugar and chow as consumed by rats on a fcHFHS diet.

Results: After i.p. injection of leptin, rats on a chow, fcHF or fcHS diet significantly reduced food intake, whereas rats on a fcHFHS diet showed leptin resistance. On the contrary, upon i.c.v. injection, the fcHFHS group did respond to leptin and showed increased sensitivity when food intake was measured over 24 h. In the second experiment, again we observed leptin resistance to i.p. injections in rats on a fcHFHS, while the rats on a ncHFHS diet remained sensitive to leptin and significantly reduced their food intake.

Conclusion: The fcHFHS diet results in leptin resistance peripherally but not centrally. Furthermore, the choice component is important for the peripheral leptin resistance that results from the fcHFHS diet.