Maternal Exercise Mediates Hepatic Metabolic Programming via Activation of AMPK-PGC1α Axis in the Offspring of Obese Mothers
Philipp Kasper,
Saida Breuer,
Thorben Hoffmann,
Christina Vohlen,
Ruth Janoschek,
Lisa Schmitz,
Sarah Appel,
Gregor Fink,
Christoph Hünseler,
Alexander Quaas,
Münevver Demir,
Sonja Lang,
Hans-Michael Steffen,
Anna Martin,
Christoph Schramm,
Martin Bürger,
Esther Mahabir,
Tobias Goeser,
Jörg Dötsch,
Eva Hucklenbruch-Rother,
Inga Bae-Gartz
Affiliations
Philipp Kasper
Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Saida Breuer
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Thorben Hoffmann
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Christina Vohlen
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Ruth Janoschek
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Lisa Schmitz
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Sarah Appel
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Gregor Fink
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Christoph Hünseler
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Alexander Quaas
Department of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Münevver Demir
Charité Campus Mitte and Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, D-13353 Berlin, Germany
Sonja Lang
Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Hans-Michael Steffen
Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Anna Martin
Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Christoph Schramm
Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Martin Bürger
Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Esther Mahabir
Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, D-50937 Cologne, Germany
Tobias Goeser
Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Jörg Dötsch
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Eva Hucklenbruch-Rother
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Inga Bae-Gartz
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
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-γ-coactivator-1α (PGC-1α)-signaling. Offspring of exercised dams exhibited a comparable hepatic metabolic signature to their mothers with increased AMPK-PGC1α-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.
