title: Leptin-receptor-expressing neurons in the dorsomedial hypothalamus and median preoptic area regulate sympathetic brown adipose tissue circuits.
abstract: 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.
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ilan A
authors.initials: IA
authors.lastname: Kerman
authors.forename: Amanda
authors.initials: A
authors.lastname: Laque
authors.forename: Phillip
authors.initials: P
authors.lastname: Nguyen
authors.forename: Miro
authors.initials: M
authors.lastname: Faouzi
authors.forename: Gwendolyn W
authors.initials: GW
authors.lastname: Louis
authors.forename: Justin C
authors.initials: JC
authors.lastname: Jones
authors.forename: Chris
authors.initials: C
authors.lastname: Rhodes
authors.forename: Heike
authors.initials: H
authors.lastname: Münzberg
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature; D003080:Cold Temperature; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism*; D011558:Herpesvirus 1, Suid; D007150:Immunohistochemistry; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011301:Preoptic Area / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System; D013569:Synapses / Q000378:metabolism
chemical_list: D020738:Leptin; D016760:Proto-Oncogene Proteins c-fos; D054411:Receptors, Leptin