Exercise Improves Outcomes of Surgery on Fatty Liver in Mice: A Novel Effect Mediated by the AMPK Pathway.

Linecker, Michael; Frick, Lukas; Kron, Philipp; Limani, Perparim; Kambakamba, Patryk; Tschuor, Christoph; Langiewicz, Magda; Kachaylo, Ekaterina; Tian, Yinghua; Schneider, Marcel A; Ungethüm, Udo; Calo, Nicolas; Foti, Michelangelo; Dufour, Jean-François; Graf, Rolf; Humar, Bostjan; Clavien, Pierre-Alain (2018). Exercise Improves Outcomes of Surgery on Fatty Liver in Mice: A Novel Effect Mediated by the AMPK Pathway. (In Press). Annals of surgery Lippincott Williams & Wilkins 10.1097/SLA.0000000000002904

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OBJECTIVE To investigate whether exercise improves outcomes of surgery on fatty liver, and whether pharmacological approaches can substitute exercising programs. SUMMARY OF BACKGROUND DATA Steatosis is the hepatic manifestation of the metabolic syndrome, and decreases the liver's ability to handle inflammatory stress or to regenerate after tissue loss. Exercise activates adenosine monophosphate-activated kinase (AMPK) and mitigates steatosis; however, its impact on ischemia-reperfusion injury and regeneration is unknown. METHODS We used a mouse model of simple, diet-induced steatosis and assessed the impact of exercise on metabolic parameters, ischemia-reperfusion injury and regeneration after hepatectomy. The same parameters were evaluated after treatment of mice with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Mice on a control diet served as age-matched controls. RESULTS A 4-week-exercising program reversed steatosis, lowered insulin levels, and improved glucose tolerance. Exercise markedly enhanced the ischemic tolerance and the regenerative capacity of fatty liver. Replacing exercise with AICAR was sufficient to replicate the above benefits. Both exercise and AICAR improved survival after extended hepatectomy in mice challenged with a Western diet, indicating protection from resection-induced liver failure. CONCLUSIONS Exercise efficiently counteracts the metabolic, ischemic, and regenerative deficits of fatty liver. AICAR acts as an exercise mimetic in settings of fatty liver disease, an important finding given the compliance issues associated with exercise. Exercising, or its substitution through AICAR, may provide a feasible strategy to negate the hepatic consequences of energy-rich diet, and has the potential to extend the application of liver surgery if confirmed in humans.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Dufour, Jean-François

Subjects:

600 Technology
600 Technology > 610 Medicine & health

ISSN:

0003-4932

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

28 Sep 2018 14:08

Last Modified:

23 Aug 2019 02:30

Publisher DOI:

10.1097/SLA.0000000000002904

PubMed ID:

30138163

BORIS DOI:

10.7892/boris.120167

URI:

https://boris.unibe.ch/id/eprint/120167

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