Universität zu Köln

Kasper, Philipp ORCID: 0000-0002-6218-2239, Breuer, Saida, Hoffmann, Thorben, Vohlen, Christina, Janoschek, Ruth, Schmitz, Lisa, Appel, Sarah, Fink, Gregor, Huenseler, Christoph, Quaas, Alexander, Demir, Muenevver, Lang, Sonja, Steffen, Hans-Michael, Martin, Anna, Schramm, Christoph, Buerger, Martin, Mahabir, Esther, Goeser, Tobias, Doetsch, Joerg, Hucklenbruch-Rother, Eva and Bae-Gartz, Inga (2021). Maternal Exercise Mediates Hepatic Metabolic Programming via Activation of AMPK-PGC1 alpha Axis in the Offspring of Obese Mothers. Cells, 10 (5). BASEL: MDPI. ISSN 2073-4409

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Abstract

Maternal obesity is associated with an increased risk of hepatic metabolic dysfunction for both mother and offspring and targeted interventions to address this growing metabolic disease burden are urgently needed. This study investigates whether maternal exercise (ME) could reverse the detrimental effects of hepatic metabolic dysfunction in obese dams and their offspring while focusing on the AMP-activated protein kinase (AMPK), representing a key regulator of hepatic metabolism. In a mouse model of maternal western-style-diet (WSD)-induced obesity, we established an exercise intervention of voluntary wheel-running before and during pregnancy and analyzed its effects on hepatic energy metabolism during developmental organ programming. ME prevented WSD-induced hepatic steatosis in obese dams by alterations of key hepatic metabolic processes, including activation of hepatic ss-oxidation and inhibition of lipogenesis following increased AMPK and peroxisome-proliferator-activated-receptor-gamma-coactivator-1 alpha (PGC-1 alpha)-signaling. Offspring of exercised dams exhibited a comparable hepatic metabolic signature to their mothers with increased AMPK-PGC1 alpha-activity and beneficial changes in hepatic lipid metabolism and were protected from WSD-induced adipose tissue accumulation and hepatic steatosis in later life. In conclusion, this study demonstrates that ME provides a promising strategy to improve the metabolic health of both obese mothers and their offspring and highlights AMPK as a potential metabolic target for therapeutic interventions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kasper, Philipp UNSPECIFIED orcid.org/0000-0002-6218-2239 UNSPECIFIED Breuer, Saida UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Thorben UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoschek, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Appel, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gregor UNSPECIFIED UNSPECIFIED UNSPECIFIED Huenseler, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Demir, Muenevver UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Steffen, Hans-Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Schramm, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Buerger, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Mahabir, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Goeser, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Bae-Gartz, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-592773
DOI:	10.3390/cells10051247
Journal or Publication Title:	Cells
Volume:	10
Number:	5
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BODY-MASS INDEX; FATTY LIVER; NONALCOHOLIC STEATOHEPATITIS; PREGNANCY MECHANISMS; PROTEIN-KINASE; PPAR-GAMMA; AMPK; HEALTH; METFORMIN; DISEASE Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59277