RT Journal Article
SR Electronic
T1 Leptin-Receptor-Expressing Neurons in the Dorsomedial Hypothalamus and Median Preoptic Area Regulate Sympathetic Brown Adipose Tissue Circuits
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1873
OP 1884
DO 10.1523/JNEUROSCI.3223-10.2011
VO 31
IS 5
A1 Yan Zhang
A1 Ilan A. Kerman
A1 Amanda Laque
A1 Phillip Nguyen
A1 Miro Faouzi
A1 Gwendolyn W. Louis
A1 Justin C. Jones
A1 Chris Rhodes
A1 Heike Münzberg
YR 2011
UL http://www.jneurosci.org/content/31/5/1873.abstract
AB 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 (Trayhurn et al., 1976). 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 (Dimicco and Zaretsky, 2007; Morrison et al., 2008). 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 (Dimicco and Zaretsky, 2007; Morrison et al., 2008). Thus, these data present strong evidence that LepRb neurons in the DMH/DHA and mPOA mediate thermoregulatory leptin action.