Adipocyte glucocorticoid receptors mediate fat-to-brain signaling

PSYCHONEUROENDOCRINOLOGY

卷:56

Article

de Kloet, Annette D.^1,2,3  Krause, Eric G.⁴  Solomon, Matia B.¹  Flak, Jonathan N.^1,2  Scott, Karen A.^1,2  Kim, Dong-Hoon⁵  Myers, Brent¹  Ulrich-Lai, Yvonne M.¹  Woods, Stephen C.¹  Seeley, Randy J.⁶  Herman, James P.¹ 

[1] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45237 USA

[2] Univ Cincinnati, Grad Program Neurosci, Cincinnati, OH 45237 USA

[3] Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32611 USA

[4] Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USA

[5] Korea Univ, Coll Med, Dept Pharmacol, Seoul 136705, South Korea

[6] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA

关键词: Hypothalamic-pituitary-adrenal axis;    Corticosterone;    Adipose;    Obesity;    Stress;   

DOI  :  10.1016/j.psyneuen.2015.03.008

来源: Elsevier

【 摘 要 】

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. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

Free