title: Leptin receptor neurons in the dorsomedial hypothalamus are key regulators of energy expenditure and body weight, but not food intake.
abstract: OBJECTIVE
  Leptin responsive neurons play an important role in energy homeostasis, controlling specific autonomic, behavioral, and neuroendocrine functions. We have previously identified a population of leptin receptor (LepRb) expressing neurons within the dorsomedial hypothalamus/dorsal hypothalamic area (DMH/DHA) which are related to neuronal circuits that control brown adipose tissue (BAT) thermogenesis. Intra-DMH leptin injections also activate sympathetic outflow to BAT, but whether such effects are mediated directly via DMH/DHA LepRb neurons and whether this is physiologically relevant for whole body energy expenditure and body weight regulation has yet to be determined.
  
  
  METHODS
  We used pharmacosynthetic receptors (DREADDs) to selectively activate DMH/DHA LepRb neurons. We further deleted LepRb with virally driven cre-recombinase from DMH/DHA neurons and determined the physiological importance of DMH/DHA LepRb neurons in whole body energy homeostasis.
  
  
  RESULTS
  Neuronal activation of DMH/DHA LepRb neurons with DREADDs promoted BAT thermogenesis and locomotor activity, which robustly induced energy expenditure (p < 0.001) and decreases body weight (p < 0.001). Similarly, intra-DMH/DHA leptin injections normalized hypothermia and attenuated body weight gain in leptin-deficient ob/ob mice. Conversely, ablation of LepRb from DMH/DHA neurons remarkably drives weight gain (p < 0.001) by reducing energy expenditure (p < 0.001) and locomotor activity (p < 0.001). The observed changes in body weight were largely independent of food intake.
  
  
  CONCLUSIONS
  Taken together, our data highlight that DMH/DHA LepRb neurons are sufficient and necessary to regulate energy expenditure and body weight.
authors.affiliation: Central Leptin Signaling, Pennington Biomedical Research Center (PBRC), LSU System, Baton Rouge, LA, USA.
authors.forename: Kavon
authors.initials: K
authors.lastname: Rezai-Zadeh
authors.affiliation: Central Leptin Signaling, Pennington Biomedical Research Center (PBRC), LSU System, Baton Rouge, LA, USA.
authors.forename: Sanghou
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Physiology, School of Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Central Leptin Signaling, Pennington Biomedical Research Center (PBRC), LSU System, Baton Rouge, LA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Laque
authors.affiliation: Central Leptin Signaling, Pennington Biomedical Research Center (PBRC), LSU System, Baton Rouge, LA, USA.
authors.forename: Candice
authors.initials: C
authors.lastname: Schwartzenburg
authors.affiliation: Neurosignaling, Pennington Biomedical Research Center (PBRC), LSU System, Baton Rouge, LA, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Morrison
authors.affiliation: Department of Physiology, School of Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Derbenev
authors.affiliation: Department of Physiology, School of Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zsombok
authors.affiliation: Central Leptin Signaling, Pennington Biomedical Research Center (PBRC), LSU System, Baton Rouge, LA, USA.
authors.forename: Heike
authors.initials: H
authors.lastname: Münzberg
keywords: DREADD; Dorsomedial hypothalamus; Energy expenditure; Leptin; Thermoregulation