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Moderate Treadmill Exercise Alleviates NAFLD by Regulating the Biogenesis and Autophagy of Lipid Droplet.
Nutrients. 2022 Nov 20; 14(22)N

Abstract

Lipid droplet is a dynamic organelle that undergoes periods of biogenesis and degradation under environmental stimuli. The excessive accumulation of lipid droplets is the major characteristic of non-alcoholic fatty liver disease (NAFLD). Moderate aerobic exercise is a powerful intervention protecting against the progress of NAFLD. However, its impact on lipid droplet dynamics remains ambiguous. Mice were fed with 15 weeks of high-fat diet in order to induce NAFLD. Meanwhile, the mice performed 15 weeks of treadmill exercise. Our results showed that 15 weeks of regular moderate treadmill exercise alleviated obesity, insulin intolerance, hyperlipidemia, and hyperglycemia induced by HFD. Importantly, exercise improved histological phenotypes of NAFLD, including hepatic steatosis, inflammation, and locular ballooning, as well as prevented liver fat deposition and liver injury induced by HFD. Exercise reduced hepatic lipid droplet size, and moreover, it reduced PLIN2 protein level and increased PLIN3 protein level in the liver of HFD mice. Interestingly, our results showed that exercise did not significantly affect the gene expressions of DGAT1, DGAT2, or SEIPIN, which were involved in TG synthesis. However, it did reduce the expressions of FITM2, CIDEA, and FSP27, which were major involved in lipid droplet growth and budding, and lipid droplet expansion. In addition, exercise reduced ATGL protein level in HFD mice, and regulated lipophagy-related markers, including increasing ATG5, LAMP1, LAMP2, LAL, and CTSD, decreasing LC3II/I and p62, and promoting colocalization of LAMP1 with LDs. In summary, our data suggested that 15 weeks of moderate treadmill exercise was beneficial for regulating liver lipid droplet dynamics in HFD mice by inhibiting abnormal lipid droplets expansion and enhancing clearance of lipid droplets by lysosomes during the lipophagic process, which might provide highly flexible turnover for lipid mobilization and metabolism. Abbreviations: β-actin: actin beta; ATG5: autophagy related 5; LAMP2: lysosomal-associated membrane protein 2; LAMP1: lysosomal-associated membrane protein 1; SQSTM1/p62: sequestosome 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ATGL: adipose triglyceride lipase; CSTD: cathepsin D; LAL: lysosomal acid lipase; DGAT1: diacylglycerol-o-acyltransferase 1; DGAT2: diacylglycerol-o-acyltransferase 2; CIDEA: cell death inducing dffa-like effector a; CIDEC/FSP27: cell death inducing dffa-like effector c; FITM2: fat storage-inducing transmembrane protein 2; PLIN2: adipose differentiation related protein; PLN3: tail-interacting protein 47; HSP90: heat shock protein 90; SREBP1c: sterol regulatory element binding protein-1c; chREBP: carbohydrate response element binding protein.

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Authors+Show Affiliations

Yang Y
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Li X
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Liu Z
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Ruan X
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Wang H
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Zhang Q
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Cao L
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Song L
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Chen Y
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.
Sun Y
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China. College of Physical Education and Health, East China Normal University, Shanghai 200241, China.

MeSH

MiceAnimalsNon-alcoholic Fatty Liver DiseaseLipid DropletsDiglyceridesAutophagyPerilipin-2Sterol Regulatory Element Binding Protein 1Diacylglycerol O-Acyltransferase

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36432597

Citation

Yang, Yangjun, et al. "Moderate Treadmill Exercise Alleviates NAFLD By Regulating the Biogenesis and Autophagy of Lipid Droplet." Nutrients, vol. 14, no. 22, 2022.
Yang Y, Li X, Liu Z, et al. Moderate Treadmill Exercise Alleviates NAFLD by Regulating the Biogenesis and Autophagy of Lipid Droplet. Nutrients. 2022;14(22).
Yang, Y., Li, X., Liu, Z., Ruan, X., Wang, H., Zhang, Q., Cao, L., Song, L., Chen, Y., & Sun, Y. (2022). Moderate Treadmill Exercise Alleviates NAFLD by Regulating the Biogenesis and Autophagy of Lipid Droplet. Nutrients, 14(22). https://doi.org/10.3390/nu14224910
Yang Y, et al. Moderate Treadmill Exercise Alleviates NAFLD By Regulating the Biogenesis and Autophagy of Lipid Droplet. Nutrients. 2022 Nov 20;14(22) PubMed PMID: 36432597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Moderate Treadmill Exercise Alleviates NAFLD by Regulating the Biogenesis and Autophagy of Lipid Droplet. AU - Yang,Yangjun, AU - Li,Xi, AU - Liu,Zonghan, AU - Ruan,Xinyu, AU - Wang,Huihui, AU - Zhang,Qiang, AU - Cao,Lu, AU - Song,Luchen, AU - Chen,Yinghong, AU - Sun,Yi, Y1 - 2022/11/20/ PY - 2022/10/01/received PY - 2022/11/13/revised PY - 2022/11/17/accepted PY - 2022/11/26/entrez PY - 2022/11/27/pubmed PY - 2022/11/30/medline KW - NAFLD KW - exercise KW - lipid droplet KW - lipid droplet biogenesis KW - lipid droplet expansion KW - lipophagy JF - Nutrients JO - Nutrients VL - 14 IS - 22 N2 - Lipid droplet is a dynamic organelle that undergoes periods of biogenesis and degradation under environmental stimuli. The excessive accumulation of lipid droplets is the major characteristic of non-alcoholic fatty liver disease (NAFLD). Moderate aerobic exercise is a powerful intervention protecting against the progress of NAFLD. However, its impact on lipid droplet dynamics remains ambiguous. Mice were fed with 15 weeks of high-fat diet in order to induce NAFLD. Meanwhile, the mice performed 15 weeks of treadmill exercise. Our results showed that 15 weeks of regular moderate treadmill exercise alleviated obesity, insulin intolerance, hyperlipidemia, and hyperglycemia induced by HFD. Importantly, exercise improved histological phenotypes of NAFLD, including hepatic steatosis, inflammation, and locular ballooning, as well as prevented liver fat deposition and liver injury induced by HFD. Exercise reduced hepatic lipid droplet size, and moreover, it reduced PLIN2 protein level and increased PLIN3 protein level in the liver of HFD mice. Interestingly, our results showed that exercise did not significantly affect the gene expressions of DGAT1, DGAT2, or SEIPIN, which were involved in TG synthesis. However, it did reduce the expressions of FITM2, CIDEA, and FSP27, which were major involved in lipid droplet growth and budding, and lipid droplet expansion. In addition, exercise reduced ATGL protein level in HFD mice, and regulated lipophagy-related markers, including increasing ATG5, LAMP1, LAMP2, LAL, and CTSD, decreasing LC3II/I and p62, and promoting colocalization of LAMP1 with LDs. In summary, our data suggested that 15 weeks of moderate treadmill exercise was beneficial for regulating liver lipid droplet dynamics in HFD mice by inhibiting abnormal lipid droplets expansion and enhancing clearance of lipid droplets by lysosomes during the lipophagic process, which might provide highly flexible turnover for lipid mobilization and metabolism. Abbreviations: β-actin: actin beta; ATG5: autophagy related 5; LAMP2: lysosomal-associated membrane protein 2; LAMP1: lysosomal-associated membrane protein 1; SQSTM1/p62: sequestosome 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ATGL: adipose triglyceride lipase; CSTD: cathepsin D; LAL: lysosomal acid lipase; DGAT1: diacylglycerol-o-acyltransferase 1; DGAT2: diacylglycerol-o-acyltransferase 2; CIDEA: cell death inducing dffa-like effector a; CIDEC/FSP27: cell death inducing dffa-like effector c; FITM2: fat storage-inducing transmembrane protein 2; PLIN2: adipose differentiation related protein; PLN3: tail-interacting protein 47; HSP90: heat shock protein 90; SREBP1c: sterol regulatory element binding protein-1c; chREBP: carbohydrate response element binding protein. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/36432597/Moderate_Treadmill_Exercise_Alleviates_NAFLD_by_Regulating_the_Biogenesis_and_Autophagy_of_Lipid_Droplet_ DB - PRIME DP - Unbound Medicine ER -