Leptin-Receptor-Expressing Neurons in the Dorsomedial Hypothalamus and Median Preoptic Area Regulate Sympathetic Brown Adipose Tissue Circuits
Open Access
- 2 February 2011
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (5), 1873-1884
- https://doi.org/10.1523/jneurosci.3223-10.2011
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.Keywords
This publication has 78 references indexed in Scilit:
- Ventral Tegmental Area Leptin Receptor Neurons Specifically Project to and Regulate Cocaine- and Amphetamine-Regulated Transcript Neurons of the Extended Central AmygdalaJournal of Neuroscience, 2010
- Dorsomedial hypothalamus mediates autonomic, neuroendocrine, and locomotor responses evoked from the medial preoptic areaAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2010
- Leptin “gates” thermogenic action of thyrotropin-releasing hormone in the hindbrainBrain Research, 2009
- Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress FeedingCell Metabolism, 2009
- Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regionsNeuroscience, 2009
- Direct Innervation of GnRH Neurons by Metabolic- and Sexual Odorant-Sensing Leptin Receptor Neurons in the Hypothalamic Ventral Premammillary NucleusJournal of Neuroscience, 2009
- The Geometry of Leptin Action in the Brain: More Complicated Than a Simple ARCCell Metabolism, 2009
- Leptin Signaling in the Nucleus Tractus Solitarii Increases Sympathetic Nerve Activity to the KidneyHypertension, 2009
- Central control of thermogenesis in mammalsExperimental Physiology, 2008
- Induction of Fos-immunoreactivity in the rat brain following disinhibition of the dorsomedial hypothalamusBrain Research, 2008