Adipocyte glucocorticoid receptors mediate fat-to-brain signaling

Annette D. de Kloet, Eric G. Krause, Matia B. Solomon, Jonathan N. Flak, Karen A. Scott, Dong Hoon Kim, Brent Myers, Yvonne M. Ulrich-Lai, Stephen C. Woods, Randy J. Seeley, James P. Herman

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)110-119
Number of pages10
Publication statusPublished - 2015 Jun 1


  • Adipose
  • Corticosterone
  • Hypothalamic-pituitary-adrenal axis
  • Obesity
  • Stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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