Resveratrol Treatment Ameliorates Leptin Resistance and Adiposity Programed by the Combined Effect of Maternal and Post‐Weaning High‐Fat Diet

Scope Prenatal high‐fat (HF) and postnatal HF diet are both associated with obesity and metabolic disturbances in adults. Leptin resistance induced by obesity limits its biological effects. The anti‐obesity mechanism of resveratrol in visceral adiposity is investigated here. Methods and results During mating and lactation, Sprague–Dawley dams are fed either control or a HF diet. Subsequently, the offspring are fed chow or an HF diet. A fifth group that received maternal/postnatal HF diet and resveratrol after weaning (HHR) is used to study the effects of resveratrol treatment. Resveratrol treatment alleviates adiposity programed by maternal and postnatal HF diet by decreasing feed intake or inducing metabolic changes. Resveratrol treatment is also found to ameliorate the decrease in SIRT1 abundance observed in retroperitoneal adipose tissue, programed by maternal and postnatal HF diet. Moreover, resveratrol therapy decreases plasma leptin level and increases leptin receptor expression in retroperitoneal adipose tissue through DNA methylation modification. Conclusion These results suggest that resveratrol can alleviate peripheral leptin resistance programed by the combined effect of prenatal and postnatal HF diet through epigenetic regulation of genes coding leptin and its receptor. It provides insights into a novel mechanism explaining the beneficial effects of resveratrol in obesity management. Prenatal and postnatal high‐fat (HF) diets have combined effects on body weight and adiposity of offspring. Resveratrol treatment ameliorates the increase of body weight/adiposity and improves the reduction of SIRT1 abundance mediated by the combined effect of maternal and postnatal HF diet in adipose tissue. Resveratrol therapy can alleviate the peripheral leptin resistance programed by prenatal and postnatal HF diet through modification of DNA methylation.