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Published in: Nutrition & Metabolism 1/2015

Open Access 01-12-2015 | Research

Exercise training improves liver steatosis in mice

Authors: Sheril Alex, Andreas Boss, Arend Heerschap, Sander Kersten

Published in: Nutrition & Metabolism | Issue 1/2015

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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is rapidly turning into the most common liver disorder worldwide. One of the strategies that has been shown to effectively improve NAFLD is regular exercise, which seems to lower steatosis partly independent of weight loss. However, limited data are available about the mechanisms involved. The aim of the present study was to identify the mechanisms underlying the effect of regular exercise on liver steatosis.

Methods

Non-obese male mice were rendered steatotic by feeding a sucrose-enriched choline-deficient diet. They were then subjected to daily treadmill running for three weeks, whereas the control mice remained sedentary.

Results

Compared to the untrained mice, trained mice showed similar adipose tissue mass but had significantly reduced size of lipid droplets in the liver coupled with a reduction in liver triglyceride content (~30 %, P < 0.05). Levels of various plasma lipid parameters and plasma glucose were similar between the trained and untrained mice, whereas levels of hepatic glycogen were significantly higher in the trained mice. Hepatic triglyceride secretion rate and de novo lipogenesis were unchanged between the two sets of mice, as were indicators of lipolysis and autophagy. Finally, whole genome expression profiling indicated a mild stimulatory effect of exercise training on PPARα-mediated regulation of oxidative metabolism, including fatty acid oxidation.

Conclusions

Taken together, our study suggests that the lowering of hepatic steatosis by repeated exercise is likely due to activation of fuel oxidation pathways in liver.
Literature
1.
go back to reference Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis. 2015;239:192–202.CrossRef Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis. 2015;239:192–202.CrossRef
2.
go back to reference Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol. 2013;28 Suppl 1:68–76.CrossRef Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol. 2013;28 Suppl 1:68–76.CrossRef
3.
go back to reference Koo SH. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis. Clin Mol Hepatol. 2013;19:210–5.CrossRef Koo SH. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis. Clin Mol Hepatol. 2013;19:210–5.CrossRef
4.
go back to reference Loria P, Lonardo A, Anania F. Liver and diabetes. A vicious circle. Hepatol Res. 2013;43:51–64.CrossRef Loria P, Lonardo A, Anania F. Liver and diabetes. A vicious circle. Hepatol Res. 2013;43:51–64.CrossRef
5.
go back to reference Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115:1343–51.CrossRef Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115:1343–51.CrossRef
6.
go back to reference Jacome-Sosa MM, Parks EJ. Fatty acid sources and their fluxes as they contribute to plasma triglyceride concentrations and fatty liver in humans. Curr Opin Lipidol. 2014;25:213–20.CrossRef Jacome-Sosa MM, Parks EJ. Fatty acid sources and their fluxes as they contribute to plasma triglyceride concentrations and fatty liver in humans. Curr Opin Lipidol. 2014;25:213–20.CrossRef
7.
go back to reference Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–65.CrossRef Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–65.CrossRef
8.
go back to reference Cariou B, Hanf R, Lambert-Porcheron S, Zair Y, Sauvinet V, Noel B, et al. Dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care. 2013;36:2923–30.CrossRef Cariou B, Hanf R, Lambert-Porcheron S, Zair Y, Sauvinet V, Noel B, et al. Dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care. 2013;36:2923–30.CrossRef
9.
go back to reference Johnson NA, George J. Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. Hepatology. 2010;52:370–81.CrossRef Johnson NA, George J. Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. Hepatology. 2010;52:370–81.CrossRef
10.
go back to reference Slentz CA, Bateman LA, Willis LH, Shields AT, Tanner CJ, Piner LW, et al. Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT. Am J Physiol Endocrinol Metab. 2011;301:E1033–9.CrossRef Slentz CA, Bateman LA, Willis LH, Shields AT, Tanner CJ, Piner LW, et al. Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT. Am J Physiol Endocrinol Metab. 2011;301:E1033–9.CrossRef
11.
go back to reference Bacchi E, Negri C, Targher G, Faccioli N, Lanza M, Zoppini G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial). Hepatology. 2013;58:1287–95.CrossRef Bacchi E, Negri C, Targher G, Faccioli N, Lanza M, Zoppini G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial). Hepatology. 2013;58:1287–95.CrossRef
12.
go back to reference Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009;50:1105–12.CrossRef Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009;50:1105–12.CrossRef
13.
go back to reference Keating SE, Hackett DA, Parker HM, O’Connor HT, Gerofi JA, Sainsbury A, et al. Effect of aerobic exercise training dose on liver fat and visceral adiposity. J Hepatol. 2015;63(1):174–82.CrossRef Keating SE, Hackett DA, Parker HM, O’Connor HT, Gerofi JA, Sainsbury A, et al. Effect of aerobic exercise training dose on liver fat and visceral adiposity. J Hepatol. 2015;63(1):174–82.CrossRef
14.
go back to reference Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;57:157–66.CrossRef Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;57:157–66.CrossRef
15.
go back to reference Green CJ, Pramfalk C, Morten KJ, Hodson L. From whole body to cellular models of hepatic triglyceride metabolism: man has got to know his limitations. Am J Physiol Endocrinol Metab. 2015;308:E1–20.CrossRef Green CJ, Pramfalk C, Morten KJ, Hodson L. From whole body to cellular models of hepatic triglyceride metabolism: man has got to know his limitations. Am J Physiol Endocrinol Metab. 2015;308:E1–20.CrossRef
16.
go back to reference Berglund ED, Lustig DG, Baheza RA, Hasenour CM, Lee-Young RS, Donahue EP, et al. Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver. Diabetes. 2011;60:2720–9.CrossRef Berglund ED, Lustig DG, Baheza RA, Hasenour CM, Lee-Young RS, Donahue EP, et al. Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver. Diabetes. 2011;60:2720–9.CrossRef
17.
go back to reference Borsting Jordy A, Kraakman MJ, Gardner T, Estevez E, Kammoun HL, Weir JM, et al. Analysis of the liver lipidome reveals insights into the protective effect of exercise on high fat diet induced hepatosteatosis in mice. Am J Physiol Endocrinol Metab. 2015;308(9):E778–91. doi:10.1152/ajpendo.00547.2014.CrossRef Borsting Jordy A, Kraakman MJ, Gardner T, Estevez E, Kammoun HL, Weir JM, et al. Analysis of the liver lipidome reveals insights into the protective effect of exercise on high fat diet induced hepatosteatosis in mice. Am J Physiol Endocrinol Metab. 2015;308(9):E778–91. doi:10.​1152/​ajpendo.​00547.​2014.CrossRef
18.
go back to reference Cho J, Lee I, Kim D, Koh Y, Kong J, Lee S, et al. Effect of aerobic exercise training on non-alcoholic fatty liver disease induced by a high fat diet in C57BL/6 mice. J Exerc Nutr Biochem. 2014;18:339–46.CrossRef Cho J, Lee I, Kim D, Koh Y, Kong J, Lee S, et al. Effect of aerobic exercise training on non-alcoholic fatty liver disease induced by a high fat diet in C57BL/6 mice. J Exerc Nutr Biochem. 2014;18:339–46.CrossRef
19.
go back to reference Cintra DE, Ropelle ER, Vitto MF, Luciano TF, Souza DR, Engelmann J, et al. Reversion of hepatic steatosis by exercise training in obese mice: the role of sterol regulatory element-binding protein-1c. Life Sci. 2012;91:395–401.CrossRef Cintra DE, Ropelle ER, Vitto MF, Luciano TF, Souza DR, Engelmann J, et al. Reversion of hepatic steatosis by exercise training in obese mice: the role of sterol regulatory element-binding protein-1c. Life Sci. 2012;91:395–401.CrossRef
20.
go back to reference Schultz A, Mendonca LS, Aguila MB, Mandarim-de-Lacerda CA. Swimming training beneficial effects in a mice model of nonalcoholic fatty liver disease. Exp Toxicol Pathol. 2012;64:273–82.CrossRef Schultz A, Mendonca LS, Aguila MB, Mandarim-de-Lacerda CA. Swimming training beneficial effects in a mice model of nonalcoholic fatty liver disease. Exp Toxicol Pathol. 2012;64:273–82.CrossRef
21.
go back to reference Vieira VJ, Valentine RJ, Wilund KR, Woods JA. Effects of diet and exercise on metabolic disturbances in high-fat diet-fed mice. Cytokine. 2009;46:339–45.CrossRef Vieira VJ, Valentine RJ, Wilund KR, Woods JA. Effects of diet and exercise on metabolic disturbances in high-fat diet-fed mice. Cytokine. 2009;46:339–45.CrossRef
22.
go back to reference Aoi W, Naito Y, Hang LP, Uchiyama K, Akagiri S, Mizushima K, et al. Regular exercise prevents high-sucrose diet-induced fatty liver via improvement of hepatic lipid metabolism. Biochem Biophys Res Commun. 2011;413:330–5.CrossRef Aoi W, Naito Y, Hang LP, Uchiyama K, Akagiri S, Mizushima K, et al. Regular exercise prevents high-sucrose diet-induced fatty liver via improvement of hepatic lipid metabolism. Biochem Biophys Res Commun. 2011;413:330–5.CrossRef
23.
go back to reference Kawanishi N, Yano H, Mizokami T, Takahashi M, Oyanagi E, Suzuki K. Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet induced-obesity in mice. Brain Behav Immun. 2012;26:931–41.CrossRef Kawanishi N, Yano H, Mizokami T, Takahashi M, Oyanagi E, Suzuki K. Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet induced-obesity in mice. Brain Behav Immun. 2012;26:931–41.CrossRef
24.
go back to reference Capozza F, Combs TP, Cohen AW, Cho YR, Park SY, Schubert W, et al. Caveolin-3 knockout mice show increased adiposity and whole body insulin resistance, with ligand-induced insulin receptor instability in skeletal muscle. Am J Physiol Cell Physiol. 2005;288:C1317–31.CrossRef Capozza F, Combs TP, Cohen AW, Cho YR, Park SY, Schubert W, et al. Caveolin-3 knockout mice show increased adiposity and whole body insulin resistance, with ligand-induced insulin receptor instability in skeletal muscle. Am J Physiol Cell Physiol. 2005;288:C1317–31.CrossRef
25.
go back to reference Delgado TC, Pinheiro D, Caldeira M, Castro MM, Geraldes CF, Lopez-Larrubia P, et al. Sources of hepatic triglyceride accumulation during high-fat feeding in the healthy rat. NMR Biomed. 2009;22:310–7.CrossRef Delgado TC, Pinheiro D, Caldeira M, Castro MM, Geraldes CF, Lopez-Larrubia P, et al. Sources of hepatic triglyceride accumulation during high-fat feeding in the healthy rat. NMR Biomed. 2009;22:310–7.CrossRef
26.
go back to reference Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226:497–509. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226:497–509.
27.
go back to reference Jones JG, Merritt M, Malloy C. Quantifying tracer levels of (2)H(2)O enrichment from microliter amounts of plasma and urine by (2)H NMR. Magn Reson Med. 2001;45:156–8.CrossRef Jones JG, Merritt M, Malloy C. Quantifying tracer levels of (2)H(2)O enrichment from microliter amounts of plasma and urine by (2)H NMR. Magn Reson Med. 2001;45:156–8.CrossRef
28.
go back to reference Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19:185–93.CrossRef Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19:185–93.CrossRef
29.
go back to reference Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP. Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 2003;31:e15.CrossRef Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP. Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 2003;31:e15.CrossRef
30.
go back to reference Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, et al. Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 2005;33:e175.CrossRef Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, et al. Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 2005;33:e175.CrossRef
31.
go back to reference Sartor MA, Tomlinson CR, Wesselkamper SC, Sivaganesan S, Leikauf GD, Medvedovic M. Intensity-based hierarchical Bayes method improves testing for differentially expressed genes in microarray experiments. BMC Bioinformatics. 2006;7:538.CrossRef Sartor MA, Tomlinson CR, Wesselkamper SC, Sivaganesan S, Leikauf GD, Medvedovic M. Intensity-based hierarchical Bayes method improves testing for differentially expressed genes in microarray experiments. BMC Bioinformatics. 2006;7:538.CrossRef
32.
go back to reference Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50.CrossRef Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50.CrossRef
33.
go back to reference Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, et al. Autophagy regulates lipid metabolism. Nature. 2009;458:1131–5.CrossRef Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, et al. Autophagy regulates lipid metabolism. Nature. 2009;458:1131–5.CrossRef
34.
go back to reference Rabol R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci U S A. 2011;108:13705–9.CrossRef Rabol R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci U S A. 2011;108:13705–9.CrossRef
35.
go back to reference Baldwin KM, Fitts RH, Booth FW, Winder WW, Holloszy JO. Depletion of muscle and liver glycogen during exercise. Protective effect of training. Pflugers Arch. 1975;354:203–12.CrossRef Baldwin KM, Fitts RH, Booth FW, Winder WW, Holloszy JO. Depletion of muscle and liver glycogen during exercise. Protective effect of training. Pflugers Arch. 1975;354:203–12.CrossRef
36.
go back to reference Hribal ML, Oriente F, Accili D. Mouse models of insulin resistance. Am J Physiol Endocrinol Metab. 2002;282:E977–81.CrossRef Hribal ML, Oriente F, Accili D. Mouse models of insulin resistance. Am J Physiol Endocrinol Metab. 2002;282:E977–81.CrossRef
37.
go back to reference Bultot L, Guigas B, Von Wilamowitz-Moellendorff A, Maisin L, Vertommen D, Hussain N, et al. AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase. Biochem J. 2012;443:193–203.CrossRef Bultot L, Guigas B, Von Wilamowitz-Moellendorff A, Maisin L, Vertommen D, Hussain N, et al. AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase. Biochem J. 2012;443:193–203.CrossRef
38.
go back to reference Assifi MM, Suchankova G, Constant S, Prentki M, Saha AK, Ruderman NB. AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats. Am J Physiol Endocrinol Metab. 2005;289:E794–800.CrossRef Assifi MM, Suchankova G, Constant S, Prentki M, Saha AK, Ruderman NB. AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats. Am J Physiol Endocrinol Metab. 2005;289:E794–800.CrossRef
39.
go back to reference Plaisance EP, Grandjean PW, Mahurin AJ. Independent and combined effects of aerobic exercise and pharmacological strategies on serum triglyceride concentrations: a qualitative review. Phys Sportsmed. 2009;37:11–9.CrossRef Plaisance EP, Grandjean PW, Mahurin AJ. Independent and combined effects of aerobic exercise and pharmacological strategies on serum triglyceride concentrations: a qualitative review. Phys Sportsmed. 2009;37:11–9.CrossRef
40.
go back to reference Kersten S. Physiological regulation of lipoprotein lipase. Biochim Biophys Acta. 1841;2014:919–33. Kersten S. Physiological regulation of lipoprotein lipase. Biochim Biophys Acta. 1841;2014:919–33.
41.
go back to reference Gill JM, Hardman AE. Exercise and postprandial lipid metabolism: an update on potential mechanisms and interactions with high-carbohydrate diets (review). J Nutr Biochem. 2003;14:122–32.CrossRef Gill JM, Hardman AE. Exercise and postprandial lipid metabolism: an update on potential mechanisms and interactions with high-carbohydrate diets (review). J Nutr Biochem. 2003;14:122–32.CrossRef
42.
go back to reference Catoire M, Alex S, Paraskevopulos N, Mattijssen F, Evers-van Gogh I, Schaart G, et al. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise. Proc Natl Acad Sci U S A. 2014;111:E1043–52.CrossRef Catoire M, Alex S, Paraskevopulos N, Mattijssen F, Evers-van Gogh I, Schaart G, et al. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise. Proc Natl Acad Sci U S A. 2014;111:E1043–52.CrossRef
43.
go back to reference de Wit NJ, Afman LA, Mensink M, Muller M. Phenotyping the effect of diet on non-alcoholic fatty liver disease. J Hepatol. 2012;57:1370–3.CrossRef de Wit NJ, Afman LA, Mensink M, Muller M. Phenotyping the effect of diet on non-alcoholic fatty liver disease. J Hepatol. 2012;57:1370–3.CrossRef
Metadata
Title
Exercise training improves liver steatosis in mice
Authors
Sheril Alex
Andreas Boss
Arend Heerschap
Sander Kersten
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Nutrition & Metabolism / Issue 1/2015
Electronic ISSN: 1743-7075
DOI
https://doi.org/10.1186/s12986-015-0026-1

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