Lateral thinking about leptin: A review of leptin action via the lateral hypothalamus

The lateral hypothalamic area (LHA) was initially described as a “feeding center” but we are now beginning to understand that the LHA contributes to other aspects of physiology as well. Indeed, the best-characterized neuronal populations of the LHA (which contain melanin-concentrating hormone (MCH) or the hypocretins/orexins (OX)) are not strictly orexigenic, but also have roles in regulation of the autonomic and sympathetic nervous systems as well as in modulating motivated behavior. Leptin is an anorectic hormone that regulates energy homeostasis and the mesolimbic DA system (which transduces the wanting of food, drugs of abuse, and sex) in part, via actions at the LHA. At least three populations of LHA neurons are regulated by leptin: those containing MCH, OX or the long form of the leptin receptor, LepRb. The emerging picture of leptin interaction with these LHA populations suggests that the LHA is not merely regulating feeding, but is a crucial integrator of energy balance and motivated behavior.

Research highlights
► The Lateral Hypothalamic Area (LHA) is not just a “feeding center” but a “motivation modulation center”.
► Leptin is an anorectic hormone that modulates energy homeostasis and motivated behavior.
► MCH and Orexin neurons of the LHA regulate the mesolimbic dopamine system and motivated behavior.
► Leptin regulates LHA neurons to integrate energy balance and DA signaling.