Leptin controls adiponectin production via the hypothalamus

Adipocyte generated endocrine signals, including leptin and adiponectin, control systemic insulin sensitivity as part of a broader control mechanism in energy balance. Leptin and adiponectin are inversely regulated in vivo, but not in vitro, suggesting that the inverse relationship is mediated via indirect mechanisms. The cytokine TNF-alpha has been proposed as a putative candidate in the reciprocal regulation of adiponectin and leptin. However, several recent findings, including the observation that adiponectin production is paradoxically increased in mouse models with selective hypothalamic leptin resistance, indicate that part of the inverse relationship between leptin and adiponectin is mediated via a neural interface. Therefore, we propose that adiponectin production is, at least in part, controlled by the hypothalamic actions of leptin.