Universität zu Köln

Geibel, Mirjam ORCID: 0000-0002-9697-6408, Badurek, Sylvia ORCID: 0000-0003-0808-2920, Horn, Jacqueline M., Vatanashevanopakorn, Chinnavuth ORCID: 0000-0002-4911-9227, Koudelka, Juraj, Wunderlich, Claudia M., Broenneke, Hella S., Wunderlich, F. Thomas and Minichiello, Liliana (2014). Ablation of TrkB signalling in CCK neurons results in hypercortisolism and obesity. Nat. Commun., 5. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity leads to debilitating neuroendocrine or metabolic disorders such as Cushing's syndrome (CS). Glucocorticoids control HPA axis activity through negative feedback to the pituitary gland and the central nervous system (CNS). However, the cellular mechanisms involved are poorly understood, particularly in the CNS. Here we show that, in mice, selective loss of TrkB signalling in cholecystokinin (CCK)-GABAergic neurons induces glucocorticoid resistance, resulting in increased corticotrophin-releasing hormone expression, chronic hypercortisolism, adrenocortical hyperplasia, glucose intolerance and mature-onset obesity, reminiscent of the human CS phenotype. Interestingly, obesity is not due to hyperphagia or decreased energy expenditure, but is associated with increased de novo lipogenesis in the liver. Our study therefore identifies CCK neurons as a novel and critical cellular component of the HPA axis, and demonstrates the requirement of TrkB for the transmission of glucocorticoid signalling.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Geibel, Mirjam UNSPECIFIED orcid.org/0000-0002-9697-6408 UNSPECIFIED Badurek, Sylvia UNSPECIFIED orcid.org/0000-0003-0808-2920 UNSPECIFIED Horn, Jacqueline M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vatanashevanopakorn, Chinnavuth UNSPECIFIED orcid.org/0000-0002-4911-9227 UNSPECIFIED Koudelka, Juraj UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, Claudia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Broenneke, Hella S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Minichiello, Liliana UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-445516
DOI:	10.1038/ncomms4427
Journal or Publication Title:	Nat. Commun.
Volume:	5
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MESSENGER-RNA EXPRESSION; PITUITARY-ADRENAL-AXIS; GLUCOCORTICOID-RECEPTOR; NEUROTROPHIC FACTOR; PARAVENTRICULAR NUCLEUS; MODULATES BDNF; CHRONIC STRESS; FOOD-INTAKE; HPA AXIS; BRAIN Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44551