title: Adipocyte glucocorticoid receptors mediate fat-to-brain signaling.
abstract: Stress-related (e.g., depression) and metabolic pathologies (e.g., obesity) are important and often co-morbid public health concerns. Here we identify a connection between peripheral glucocorticoid receptor (GR) signaling originating in fat with the brain control of both stress and metabolism. Mice with reduced adipocyte GR hypersecrete glucocorticoids following acute psychogenic stress and are resistant to diet-induced obesity. This hypersecretion gives rise to deficits in responsiveness to exogenous glucocorticoids, consistent with reduced negative feedback via adipocytes. Increased stress reactivity occurs in the context of elevated hypothalamic expression of hypothalamic-pituitary-adrenal (HPA) axis-excitatory neuropeptides and in the absence of altered adrenal sensitivity, consistent with a central cite of action. Our results identify a novel mechanism whereby activation of the adipocyte GR promotes peripheral energy storage while inhibiting the HPA axis, and provide functional evidence for a fat-to-brain regulatory feedback network that serves to regulate not just homeostatic energy balance but also responses to psychogenic stimuli.
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA; Graduate Program in Neuroscience, University of Cincinnati, Cincinnati, 45237, USA; Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32611, USA. Electronic address: adekloet@ufl.edu.
authors: Annette D
authors: AD
authors: de Kloet
authors: Department of Pharmacodynamics, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.
authors: Eric G
authors: EG
authors: Krause
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors: Matia B
authors: MB
authors: Solomon
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA; Graduate Program in Neuroscience, University of Cincinnati, Cincinnati, 45237, USA.
authors: Jonathan N
authors: JN
authors: Flak
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA; Graduate Program in Neuroscience, University of Cincinnati, Cincinnati, 45237, USA.
authors: Karen A
authors: KA
authors: Scott
authors: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors: Dong-Hoon
authors: DH
authors: Kim
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors: Brent
authors: B
authors: Myers
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors: Yvonne M
authors: YM
authors: Ulrich-Lai
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors: Stephen C
authors: SC
authors: Woods
authors: Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors: Randy J
authors: RJ
authors: Seeley
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA. Electronic address: james.herman@uc.edu.
authors: James P
authors: JP
authors: Herman
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D001921:Brain / Q000502:physiology*; D004032:Diet; D059305:Diet, High-Fat; D004435:Eating; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: Adipose; Corticosterone; Hypothalamic–pituitary–adrenal axis; Obesity; Stress