Universität zu Köln

Litzenburger, Thorsten, Huber, Eva-Kristina ORCID: 0000-0002-4895-962X, Dinger, Katharina, Wilke, Rebecca, Vohlen, Christina, Selle, Jaco, Kadah, Mazlum, Persigehl, Thorsten, Heneweer, Carola, Dötsch, Jörg ORCID: 0000-0003-1529-7647 and Alejandre Alcázar, Miguel Angel ORCID: 0000-0002-3176-0411 (2020). Maternal high-fat diet induces long-term obesity with sex-dependent metabolic programming of adipocyte differentiation, hypertrophy and dysfunction in the offspring. Clinical Science, 134. pp. 921-940. London: PORTLAND PRESS LTD. ISSN 1470-8736

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Abstract

Maternal obesity determines obesity and metabolic diseases in the offspring. The white adipose tissue (WAT) orchestrates metabolic pathways, and its dysfunction contributes to metabolic disorders in a sex-dependent manner. Here, we tested if sex differences influence the molecular mechanisms of metabolic programming of WAT in offspring of obese dams. To this end, maternal obesity was induced with high-fat diet (HFD) and the offspring were studied at an early phase [postnatal day 21 (P21)], a late phase (P70) and finally P120. In the early phase we found a sex-independent increase in WAT in offspring of obese dams using magnetic resonance imaging (MRI), which was more pronounced in females than males. While the adipocyte size increased in both sexes, the distribution of WAT differed in males and females. As mechanistic hints, we identified an inflammatory response in females and a senescence-associated reduction in the preadipocyte factor DLK in males. In the late phase, the obese body composition persisted in both sexes, with a partial reversal in females. Moreover, female offspring recovered completely from both the adipocyte hypertrophy and the inflammatory response. These findings were linked to a dysregulation of lipolytic, adipogenic and sternness-related markers as well as AMPK alpha and Akt signaling. Finally, the sex-dependent metabolic programming persisted with sex-specific differences in adipocyte size until P120. In conclusion, we do not only provide new insights into the molecular mechanisms of sex-dependent metabolic programming of WAT dysfunction, but also highlight the sex-dependent development of low- and high-grade pathogenic obesity.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Litzenburger, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Huber, Eva-Kristina hubere@smail.uni-koeln.de https://orcid.org/0000-0002-4895-962X UNSPECIFIED Dinger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilke, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Selle, Jaco UNSPECIFIED UNSPECIFIED UNSPECIFIED Kadah, Mazlum UNSPECIFIED UNSPECIFIED UNSPECIFIED Persigehl, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Heneweer, Carola UNSPECIFIED UNSPECIFIED UNSPECIFIED Dötsch, Jörg UNSPECIFIED https://orcid.org/0000-0003-1529-7647 UNSPECIFIED Alejandre Alcázar, Miguel Angel UNSPECIFIED https://orcid.org/0000-0002-3176-0411 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-651451
Identification Number:	10.1042/CS20191229
Journal or Publication Title:	Clinical Science
Volume:	134
Page Range:	pp. 921-940
Date:	17 April 2020
Publisher:	PORTLAND PRESS LTD
Place of Publication:	London
ISSN:	1470-8736
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Kinder- und Jugendmedizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language metabolic programming UNSPECIFIED maternal obesity UNSPECIFIED high-fat-diet UNSPECIFIED adipogenesis UNSPECIFIED adipocytokine UNSPECIFIED adipose tissue inflammation UNSPECIFIED
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/65145