The effects of weight cycling on serum leptin levels and lipogenic enzyme activities in adipose tissue.

Weight cycling is one of the widely used weight reduction strategies; however, the adverse effects of this method include regaining significant amounts of weight. The molecular mechanisms underlying weight gain following cycles of dietary deprivation and refeeding are still poorly understood. One of the possibilities is that repeated loss and gain of weight may promote fat deposition in adipose tissue. To test this hypothesis we investigated serum leptin levels and lipogenic enzyme activities in white adipose tissue (WAT) of male Wistar rats during 12 days of ad libitum feeding following multiple cycles of alternating food deprivation and refeeding. Rats subjected to eight cycles of food deprivation and refeeding (MFR group) showed significantly decreased circulating leptin levels when compared with control rats (nearly 50% decrease in leptin levels, P < 0.01). Throughout 12 days of ad libitum feeding, serum leptin levels increased modestly but remained significantly (24%, P < 0.05) lower than control levels. Fatty acid synthase (FAS) and malic enzyme (ME) activities (chosen as representatives of enzymes directly involved in fatty acid synthesis) were found to be considerably higher in WAT of MFR rats refed for 3 days in comparison to control rats, and remained elevated even after 12 days of refeeding. These observations suggest that the elevation of lipogenic enzyme activities induced by multiple cycles of dietary deprivation followed by refeeding persists for several days, markedly increasing the lipogenic capacity of adipose tissue, which, accompanied by a decrease in circulating leptin levels, may promote weight gain.