Obesity is a medical condition associated with metabolic disorders and low-grade systemic inflammation. Another characterizing feature of obesity is high circulating levels of leptin (a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance), a phenomenon termed hyperleptinemia. Hyperleptinemia is associated with both low-grade systemic inflammation and metabolic dysfunction in obese human beings. Moreover, obesity is associated with low testosterone in men, which correlates with high body fat. The association between leptin and low testosterone could potentially be explained via the imbalanced leptin levels that results in higher estrogen levels, which further increases the aromatase activity. The increase in aromatase activity in turn reciprocally inhibits the testosterone levels and hypothalamic pituitary gonadal axis. Novel strategies are being used to treat obesity, including leptin and testosterone therapy. However, the efficacy and adverse effects of these strategies need further validation through preclinical and clinical studies. Additionally, further studies are needed to establish the molecular mechanism behind leptin-modulated changes to testosterone in obese men. This review summarizes the available literature on the role of leptin and low testosterone during obesity.
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