Universität zu Köln

Vogt, Merly C., Paeger, Lars ORCID: 0000-0001-8716-3483, Hess, Simon, Steculorum, Sophie M., Awazawa, Motoharu, Hampel, Brigitte, Neupert, Susanne, Nicholls, Hayley T., Mauer, Jan ORCID: 0000-0002-0189-5876, Hausen, A. Christine, Predel, Reinhard, Kloppenburg, Peter, Horvath, Tamas L. and Bruening, Jens C. (2014). Neonatal Insulin Action Impairs Hypothalamic Neurocircuit Formation in Response to Maternal High-Fat Feeding. Cell, 156 (3). S. 495 - 510. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

Full text not available from this repository.

Abstract

Maternal metabolic homeostasis exerts long-term effects on the offspring's health outcomes. Here, we demonstrate that maternal high-fat diet (HFD) feeding during lactation predisposes the offspring for obesity and impaired glucose homeostasis in mice, which is associated with an impairment of the hypothalamic melanocortin circuitry. Whereas the number and neuropeptide expression of anorexigenic proopiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP) neurons, electrophysiological properties of POMC neurons, and posttranslational processing of POMC remain unaffected in response to maternal HFD feeding during lactation, the formation of POMC and AgRP projections to hypothalamic target sites is severely impaired. Abrogating insulin action in POMC neurons of the offspring prevents altered POMCprojections to the preautonomic paraventricular nucleus of the hypothalamus (PVH), pancreatic parasympathetic innervation, and impaired glucosestimulated insulin secretion in response to maternal overnutrition. These experiments reveal a critical timing, when altered maternal metabolism disrupts metabolic homeostasis in the offspring via impairing neuronal projections, and show that abnormal insulin signaling contributes to this effect.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vogt, Merly C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paeger, Lars UNSPECIFIED orcid.org/0000-0001-8716-3483 UNSPECIFIED Hess, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Steculorum, Sophie M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Awazawa, Motoharu UNSPECIFIED UNSPECIFIED UNSPECIFIED Hampel, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Neupert, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Nicholls, Hayley T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauer, Jan UNSPECIFIED orcid.org/0000-0002-0189-5876 UNSPECIFIED Hausen, A. Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Predel, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Horvath, Tamas L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-448087
DOI:	10.1016/j.cell.2014.01.008
Journal or Publication Title:	Cell
Volume:	156
Number:	3
Page Range:	S. 495 - 510
Date:	2014
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GESTATIONAL DIABETES-MELLITUS; AUTONOMIC NERVOUS-SYSTEM; PARAVENTRICULAR NUCLEUS; APPETITE REGULATORS; GLUCOSE-HOMEOSTASIS; ENERGY HOMEOSTASIS; LEPTIN SENSITIVITY; EXPRESSING NEURONS; METABOLIC SYSTEMS; NEURITE GROWTH Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44808