Universität zu Köln

Bae-Gartz, Inga, Janoschek, Ruth, Breuer, Saida, Schmitz, Lisa, Hoffmann, Thorben, Ferrari, Nina, Branik, Lena, Oberthuer, Andre, Kloppe, Cora-Sophia, Appel, Sarah, Vohlen, Christina, Doetsch, Joerg and Hucklenbruch-Rother, Eva (2019). Maternal Obesity Alters Neurotrophin-Associated MAPK Signaling in the Hypothalamus of Male Mouse Offspring. Front. Neurosci., 13. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-453X

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Abstract

Purpose: Maternal obesity has emerged as an important risk factor for the development of metabolic disorders in the offspring. The hypothalamus as the center of energy homeostasis regulation is known to function based on complex neuronal networks that evolve during fetal and early postnatal development and maintain their plasticity into adulthood. Development of hypothalamic feeding networks and their functional plasticity can be modulated by various metabolic cues, especially in early stages of development. Here, we aimed at determining the underlying molecular mechanisms that contribute to disturbed hypothalamic network formation in offspring of obese mouse dams. Methods: Female mice were fed either a control diet (CO) or a high-fat diet (HFD) after weaning until mating and during pregnancy and gestation. Male offspring was sacrificed at postnatal day (P) 21. The hypothalamus was subjected to gene array analysis, quantitative PCR and western blot analysis. Results: P21 HFD offspring displayed increased body weight, circulating insulin levels, and strongly increased activation of the hypothalamic insulin signaling cascade with a concomitant increase in ionized calcium binding adapter molecule 1 (IBA1) expression. At the same time, the global gene expression profile in CO and HFD offspring differed significantly. More specifically, manifest influences on several key pathways of hypothalamic neurogenesis, axogenesis, and regulation of synaptic transmission and plasticity were detectable. Target gene expression analysis revealed significantly decreased mRNA expression of several neurotrophic factors and co-factors and their receptors, accompanied by decreased activation of their respective intracellular signal transduction. Conclusion: Taken together, these results suggest a potential role for disturbed neurotrophin signaling and thus impaired neurogenesis, axogenesis, and synaptic plasticity in the pathogenesis of the offspring's hypothalamic feeding network dysfunction due to maternal obesity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bae-Gartz, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoschek, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Breuer, Saida UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Thorben UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferrari, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Branik, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Oberthuer, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloppe, Cora-Sophia UNSPECIFIED UNSPECIFIED UNSPECIFIED Appel, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-141410
DOI:	10.3389/fnins.2019.00962
Journal or Publication Title:	Front. Neurosci.
Volume:	13
Date:	2019
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1662-453X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIGH-FAT DIET; ACTIVATED PROTEIN-KINASES; EARLY-LIFE ORIGINS; GROWTH-FACTOR NGF; ARCUATE NUCLEUS; SYNAPTIC PLASTICITY; ENERGY-BALANCE; FOOD-INTAKE; NEURONAL PLASTICITY; MELANOCORTIN SYSTEM Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14141