Universität zu Köln

Hausen, A. Christine, Ruud, Johan, Jiang, Hong, Hess, Simon, Varbanov, Hristo ORCID: 0000-0001-9828-8855, Kloppenburg, Peter and Bruening, Jens C. (2016). Insulin-Dependent Activation of MCH Neurons Impairs Locomotor Activity and Insulin Sensitivity in Obesity. Cell Reports, 17 (10). S. 2512 - 2522. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type- specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR Delta MCH) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions. Similarly, obesity promotes PI3 kinase signaling in these neurons, and this response is abrogated in IR Delta MCH mice. In turn, acute chemogenetic activation of MCH neurons impairs locomotor activity but not insulin sensitivity. Collectively, our experiments reveal an insulin-dependent activation of MCH neurons in obesity, which contributes via distinct mechanisms to the manifestation of impaired locomotor activity and insulin resistance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hausen, A. Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruud, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED Jiang, Hong UNSPECIFIED UNSPECIFIED UNSPECIFIED Hess, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Varbanov, Hristo UNSPECIFIED orcid.org/0000-0001-9828-8855 UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-252711
DOI:	10.1016/j.celrep.2016.11.030
Journal or Publication Title:	Cell Reports
Volume:	17
Number:	10
Page Range:	S. 2512 - 2522
Date:	2016
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MELANIN-CONCENTRATING HORMONE; HEPATIC GLUCOSE-PRODUCTION; ENERGY HOMEOSTASIS; LATERAL HYPOTHALAMUS; BODY-WEIGHT; MICE; LEPTIN; RESISTANCE; CHANNELS; BRAIN Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25271