Antiobesity effects of human soluble leptin in mice nourished with a high-fat/high fructose diet

Leptin is a hormone that regulates energy balance. Since its discovery two decades ago, several efforts have been made to fully understand its role in metabolic regulation of feeding behavior, reproduction, glucose homeostasis, immune function, bone formation, lipid metabolism, among others. Its use as a therapeutic option in obese patients is still limited due to the syndrome known as Leptin resistance. In this study, we determined that the treatment of a soluble form of human Leptin (W100E) reduced food intake, body weight and triglycerides levels, but increased HDL-cholesterol levels on obese mice subjected to high-fat/high-fructose diet. In contrast, treatment with soluble human Leptin increased food intake but did not increase body weight and total-cholesterol in mice with normal diet. When stopping the treatment with human W100ELeptin, it was detected a significant increase in body weight in all groups of mice apart from the control, indicating a rebound effect. The results contribute to the understanding of how to increase Leptin sensitivity and in consequence to overcome Leptin resistance syndrome. This might be relevant in offering more evidence of the potential use of the Leptin in the treatment against obesity and overweight conditions.