Effects of exercise on high-fat diet-induced non-alcoholic fatty liver disease and lipid metabolism in ApoE knockout mice

Wen-Ching Huang; Jin-Wei Xu; Shiming Li; Xin Er Ng; Yu-Tang Tung

doi:10.1186/s12986-022-00644-w

Effects of exercise on high-fat diet-induced non-alcoholic fatty liver disease and lipid metabolism in ApoE knockout mice

Nutr Metab (Lond). 2022 Feb 16;19(1):10. doi: 10.1186/s12986-022-00644-w.

Authors

Wen-Ching Huang¹, Jin-Wei Xu², Shiming Li³, Xin Er Ng⁴, Yu-Tang Tung^{5

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Affiliations

¹ Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei, 112, Taiwan.
² Department of Forestry, National Chung Hsing University, Taichung, 402, Taiwan.
³ Department of Food Science, Rutgers University, New Brunswick, NJ, 08901, USA.
⁴ Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, 110, Taiwan.
⁵ Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, 402, Taiwan. peggytung@nchu.edu.com.
⁶ Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, 116, Taiwan. peggytung@nchu.edu.com.
⁷ Nutrition Research Center, Taipei Medical University Hospital, Taipei, 110, Taiwan. peggytung@nchu.edu.com.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD), which is growing more common in the Western world, has become the main cause of chronic liver disease and is strongly associated with metabolism syndromes. NAFLD can indicate a wide spectrum of hepatic pathologies, ranging from simple hepatic steatosis and inflammatory non-alcoholic steatohepatitis to more severe stages of fibrosis and cirrhosis. Moreover, evidence has demonstrated that physical inactivity and westernized dietary habits may facilitate the development of NAFLD. Lipid modulation and metabolism could be important factors in the development of steatosis. Lipid species, characterized using a lipidomic approach with untargeted analysis, could provide potential biomarkers for the pathogenesis of NAFLD or therapeutic applications. Thus, in this study, the effects of exercise on the improvement of NAFLD were further investigated from a lipidomic perspective through the aspects of lipid regulation and metabolism.

Methods: Wild type (WT) C57BL/6 J and C57BL/6-ApoE^em1Narl/Narl mice were assigned to one of four groups: WT mice fed a normal chow diet (CD), apolipoprotein E (ApoE) knockout mice fed a normal CD, ApoE knockout mice fed a high-fat diet (HFD), and ApoE knockout mice fed a HFD and provided with swimming exercise. The treatments (e.g., normal diet, HFD, and exercise) were provided for 12 consecutive weeks before the growth curves, biochemistry, fat composition, pathological syndromes, and lipid profiles were determined.

Results: Exercise significantly reduced the HFD-induced obesity (weight and fat composition), adipocyte hypertrophy, liver lipid accumulation, and pathological steatosis. In addition, exercise ameliorated HFD-induced steatosis in the process of NAFLD. The lipidomic analysis revealed that the changes in plasma triglyceride (14:0/16:0/22:2), phosphatidic acid (18:0/17:2), and phosphatidylglycerol (16:0/20:2) induced by the administration of the HFD could be reversed significantly by exercise.

Conclusions: The 12-week regular exercise intervention significantly alleviated HFD-induced NAFLD through modulation of specific lipid species in plasma. This finding could elucidate the lipids effects behind the hepatic pathogenesis with exercise.

Keywords: ApoE knockout; Exercise; High-fat diet; Lipidomic; Non-alcoholic fatty liver disease.

Abstract

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