Adipocyte Leptin Signaling Regulates Glycemia and Cardiovascular Function by Enhancing Brown Adipose Tissue Thermogenesis in Obese Male Mice

Leptin is known to enhance brown adipose tissue (BAT) activity through sympathetic stimulation. However, in vitro studies suggest leptin could also act directly on adipocytes to promote lipolysis. Whether these peripheral effects of leptin are relevant to systemic metabolic control in obesity remains unclear. We addressed this question by selectively restoring leptin receptor (LEPR) expression in adipocytes of obese LEPR-conditional knockout mice. LEPR restoration selectively enhanced BAT activity in male mice, which led to improved glycemic control and cardiovascular function. These findings reveal a crucial role for BAT leptin signaling in regulating energy expenditure and glycemic and cardiovascular health, primarily in males.