Leptin Increases: Physiological Roles in the Control of Sympathetic Nerve Activity, Energy Balance, and the Hypothalamic-Pituitary-Thyroid Axis

It is well established that decreases in plasma leptin levels, as with fasting, signal starvation and elicit appropriate physiological responses, such as increasing the drive to eat and decreasing energy expenditure. These responses are mediated largely by suppression of the actions of leptin in the hypothalamus, most notably on arcuate nucleus (ArcN) orexigenic neuropeptide Y neurons and anorexic pro-opiomelanocortin neurons. However, the question addressed in this review is whether the effects of increased leptin levels are also significant on the long-term control of energy balance, despite conventional wisdom to the contrary. We focus on leptin's actions (in both lean and obese individuals) to decrease food intake, increase sympathetic nerve activity, and support the hypothalamic-pituitary-thyroid axis, with particular attention to sex differences. We also elaborate on obesity-induced inflammation and its role in the altered actions of leptin during obesity.

Automated summary

It is widely accepted that decreases in plasma leptin levels, such as during fasting, signal starvation and lead to increased hunger and decreased energy expenditure. These effects are mainly mediated by the suppression of leptin actions in the hypothalamus, particularly on orexigenic neuropeptide Y neurons and anorexic pro-opiomelanocortin neurons in the arcuate nucleus. However, this review explores whether increased leptin levels also play a significant role in long-term energy balance control, contrary to conventional wisdom. We focus on leptin's actions to decrease food intake, increase sympathetic nerve activity, and support the hypothalamic-pituitary-thyroid axis, with a particular emphasis on sex differences. We also discuss the impact of obesity-induced inflammation on leptin's actions during obesity.