Endurance exercise-mediated metabolic reshuffle attenuates high-caloric diet-induced non-alcoholic fatty liver disease

Joshua J Cook; Madeline Wei; Benny Segovia; Ludmila Cosio-Lima; Jeffrey Simpson; Scott Taylor; Yunsuk Koh; Sangho Kim; Youngil Lee

doi:10.1016/j.aohep.2022.100709

Endurance exercise-mediated metabolic reshuffle attenuates high-caloric diet-induced non-alcoholic fatty liver disease

Ann Hepatol. 2022 Jul-Aug;27(4):100709. doi: 10.1016/j.aohep.2022.100709. Epub 2022 Apr 28.

Authors

Joshua J Cook¹, Madeline Wei¹, Benny Segovia¹, Ludmila Cosio-Lima¹, Jeffrey Simpson¹, Scott Taylor², Yunsuk Koh³, Sangho Kim⁴, Youngil Lee⁵

Affiliations

¹ Molecular and Cellular Exercise Physiology Laboratory, Department of Movement Sciences and Health, Usha Kundu, MD College of Health, University of West Florida, Pensacola, FL 32514, USA.
² Department of Biology, Hal Marcus College of Science and Engineering, University of West Florida, Pensacola, FL 32514, USA.
³ Department of Health, Human Performance and Recreation, Robbins College of Human Sciences, Baylor University, Waco, TX 76798, USA.
⁴ Department of Sport Science, College of Culture and Sports, School of Global Sport Studies, Korea University, Sejong 30019, South Korea.
⁵ Molecular and Cellular Exercise Physiology Laboratory, Department of Movement Sciences and Health, Usha Kundu, MD College of Health, University of West Florida, Pensacola, FL 32514, USA. Electronic address: ylee1@uwf.edu.

PMID: 35489641
DOI: 10.1016/j.aohep.2022.100709

Abstract

Introduction and aim: Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in the United States. Metabolic distress (obese diabetes) is the main causative element of NAFLD. While there is no cure for NAFLD, endurance exercise (EEx) has emerged as a therapeutic strategy against NAFLD. However, mechanisms of EXE-induced hepatic protection especially in female subjects remain unidentified. Thus, the aim of the study is to examine molecular mechanisms of EXE-induced hepatic protection against diet-induced NAFLD in female mice.

Material and methods: Nine-week-old female C57BL/6J mice were randomly divided into three groups: normal-diet control group (CON, n=11); high-fat diet/high-fructose group (HFD/HF, n=11); and HFD/HF+EEx group (HFD/HF+EEx, n=11). The mice assigned to HFD/HF and HFD/HF+EEx groups were fed with HFD/HF for 12 weeks, after which the mice assigned to the EEx group began treadmill exercise for 12 weeks, with HFD/HF continued.

Results: EEx attenuated hepatic steatosis, reduced de novo lipogenesis (reduction in ATP-Citrate- Lyase and diacylglycerol-O-acyltransferase 1), and enhanced mitochondrial biogenesis and fatty-acid activation (oxidative phosphorylation enzymes and Acyl-CoA synthetase1). Also, EEx prevented upregulation of gluconeogenic proteins (glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphatase, and phosphoenolpyruvate-carboxykinase1), premature senescence (suppression of p53, p22, and p16, tumor-necrosis-factor-α, and interleukin-1β, and oxidative stress), and autophagy deficiency. Furthermore, EXE reversed apoptosis arrest (cleaved cysteine-dependent-aspartate-directed protease3 and Poly-(ADP-ribose)-polymerase1).

Conclusion: EEx-mediated reparations of metabolic and redox imbalance (utilization of pentose phosphate pathway), and autophagy deficiency caused by metabolic distress critically contribute to preventing/delaying severe progression of NAFLD. Also, EEx-induced anti-senescence and cell turnover are crucial protective mechanisms against NAFLD.

Keywords: Endurance exercise; Mitochondria; Non-alcoholic fatty liver disease; Oxidative stress; Senescence.

MeSH terms

Animals
Diet, High-Fat
Disease Models, Animal
Female
Humans
Liver / metabolism
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease* / etiology
Non-alcoholic Fatty Liver Disease* / prevention & control