Leptin-receptor-expressing neurons in the dorsomedial hypothalamus and median preoptic area regulate sympathetic brown adipose tissue circuits

Y Zhang, IA Kerman, A Laque, P Nguyen… - Journal of …, 2011 - Soc Neuroscience
Y Zhang, IA Kerman, A Laque, P Nguyen, M Faouzi, GW Louis, JC Jones, C Rhodes…
Journal of Neuroscience, 2011Soc Neuroscience
Brown adipose tissue (BAT) thermogenesis is critical to maintain homoeothermia and is
centrally controlled via sympathetic outputs. Body temperature and BAT activity also impact
energy expenditure, and obesity is commonly associated with decreased BAT capacity and
sympathetic tone. Severely obese mice that lack leptin or its receptor (LepRb) show
decreased BAT capacity, sympathetic tone, and body temperature and thus are unable to
adapt to acute cold exposure. LepRb-expressing neurons are found in several hypothalamic …
Brown adipose tissue (BAT) thermogenesis is critical to maintain homoeothermia and is centrally controlled via sympathetic outputs. Body temperature and BAT activity also impact energy expenditure, and obesity is commonly associated with decreased BAT capacity and sympathetic tone. Severely obese mice that lack leptin or its receptor (LepRb) show decreased BAT capacity, sympathetic tone, and body temperature and thus are unable to adapt to acute cold exposure . LepRb-expressing neurons are found in several hypothalamic sites, including the dorsomedial hypothalamus (DMH) and median preoptic area (mPOA), both critical sites to regulate sympathetic, thermoregulatory BAT circuits. Specifically, a subpopulation in the DMH/dorsal hypothalamic area (DHA) is stimulated by fever-inducing endotoxins or cold exposure (; ). Using the retrograde, transsynaptic tracer pseudorabies virus (PRV) injected into the BAT of mice, we identified PRV-labeled LepRb neurons in the DMH/DHA and mPOA (and other sites), thus indicating their involvement in the regulation of sympathetic BAT circuits. Indeed, acute cold exposure induced c-Fos (as a surrogate for neuronal activity) in DMH/DHA LepRb neurons, and a large number of mPOA LepRb neurons project to the DMH/DHA. Furthermore, DMH/DHA LepRb neurons (and a subpopulation of LepRb mPOA neurons) project and synaptically couple to rostral raphe pallidus neurons, consistent with the current understanding of BAT thermoregulatory circuits from the DMH/DHA and mPOA (; ). Thus, these data present strong evidence that LepRb neurons in the DMH/DHA and mPOA mediate thermoregulatory leptin action.
Soc Neuroscience