The leptin fragment Lep116-130 attenuates hedonic consumption and sucrose-seeking in mice

Background Increased hedonic intake of palatable and high-calorie foods is one of the leading causes of obesity and is present in eating disorders. Thus, identifying new tools to manipulate hedonic intake could open new treatments for disorders of hunger and energy balance. Leptin 116–130 (Lep 116-130 ) is a biologically active fragment of leptin, an anorectic hormone essential for controlling energy balance. Lep 116-130 can reduce the intake of standard food in rodents, but its mechanism of action remains poorly understood, and whether it reduces hedonic intake has not been tested. Methods In silico molecular docking was performed to determine the binding of Lep 116-130 to the long isoform of leptin receptor (LepRb). In vitro cellular assays were performed to determine whether Lep 116-130 increased intracellular calcium levels. Behavioral feeding tests were used to characterize the intake of standard and palatable, high-calorie food under acute and chronic administration of Lep 116-130 to leptin-deficient (ob/ob) and wild-type mice. Results In silico assays suggest Lep 116-130 was less likely to bind to LepRb than leptin, and in vitro assays showed that Lep 116-130 does not increase intracellular calcium in a hypothalamic cell line that expresses LepRb. The in vivo acute administration of Lep 116-130 did not reduce standard food intake in wild-type or ob / ob mice, but it decreased intake of high-sucrose chocolate-flavored pellets in ob / ob mice. Chronic administration of Lep 116-130 did not reduce body weight, whereas it prevented increased sucrose consumption after repeated sucrose demand tests exclusively in ob/ob mice. Conclusion Lep 116-130 can regulate hedonic food consumption in obese mice, likely without a major contribution of LepRb binding, providing a proof-of-concept of Lep 116-130 as a modulator of reward-driven intake.