Universität zu Köln

Tsaousidou, Eva ORCID: 0000-0003-2751-1911, Paeger, Lars ORCID: 0000-0001-8716-3483, Belgardt, Bengt F., Pal, Martin ORCID: 0000-0002-1563-5426, Wunderlich, Claudia M., Broenneke, Hella, Collienne, Ursel, Hampel, Brigitte, Wunderlich, F. Thomas, Schmidt-Supprian, Marc ORCID: 0000-0002-8543-6166, Kloppenburg, Peter and Bruening, Jens C. (2014). Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance. Cell Reports, 9 (4). S. 1495 - 1507. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Activation of c-Jun N-terminal kinase 1 (JNK1)- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2)-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP)-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tsaousidou, Eva UNSPECIFIED orcid.org/0000-0003-2751-1911 UNSPECIFIED Paeger, Lars UNSPECIFIED orcid.org/0000-0001-8716-3483 UNSPECIFIED Belgardt, Bengt F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pal, Martin UNSPECIFIED orcid.org/0000-0002-1563-5426 UNSPECIFIED Wunderlich, Claudia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Broenneke, Hella UNSPECIFIED UNSPECIFIED UNSPECIFIED Collienne, Ursel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hampel, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Supprian, Marc UNSPECIFIED orcid.org/0000-0002-8543-6166 UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423117
DOI:	10.1016/j.celrep.2014.10.045
Journal or Publication Title:	Cell Reports
Volume:	9
Number:	4
Page Range:	S. 1495 - 1507
Date:	2014
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOPLASMIC-RETICULUM STRESS; AMPA RECEPTOR PHOSPHORYLATION; DIET-INDUCED OBESITY; N-TERMINAL KINASE; BETA/NF-KAPPA-B; LEPTIN RESISTANCE; GLUCOSE-HOMEOSTASIS; ENERGY HOMEOSTASIS; EXPRESSING NEURONS; ER STRESS Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42311