Leptin Mediates the Increase in Blood Pressure Associated with Obesity

Obesity is associated with increased blood pressure (BP), which in turn increases the risk of cardiovascular diseases. We found that the increase in leptin levels seen in diet-induced obesity (DIO) drives an increase in BP in rodents, an effect that was not seen in animals deficient in leptin or leptin receptors (LepR). Furthermore, humans with loss-of-function mutations in leptin and the LepR have low BP despite severe obesity. Leptin’s effects on BP are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), as blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH caused a rapid reduction of BP in DIO mice, independent of changes in weight. Re-expression of LepRs in the DMH of DIO LepR-deficient mice caused an increase in BP. These studies demonstrate that leptin couples changes in weight to changes in BP in mammalian species. [Display omitted] •Leptin is the link between obesity and increased blood pressure•Leptin acts through the dorsomedial hypothalamus to increase blood pressure•Blockade of leptin signaling reduces blood pressure in obese mice•Humans with defects in leptin signaling are protected from obesity hypertension Leptin is found to be the link between obesity and increased blood pressure. Blocking leptin action reduces blood pressure in obese mice with clinical studies in humans, suggesting that defects in leptin signaling may protect against hypertension associated with obesity.