Effect of moderate exercises and curcumin on hepatic transcriptional factors associated with lipid metabolism and steatosis in elderly male rat

Minoo Shirpoor , Asghar Tofighi , Alireza Shirpoor, Masoumeh Pourjabali, Leila Chodari


Background and purpose: The specific molecular mediators involved in dyslipidemia in older people are not yet clearly understood. The current study was, thus, an attempt to investigate whether moderate aerobic exercises and curcumin administration alleviates the abnormalities caused by aging in the rats' liver.

Experimental approach: Thirty-two eight-year-old young rats were classified into five groups, namely, young control, aged control, aged-curcumin, aged-exercise, and aged-curcumin-exercise co-treatment. The rats in the exercise groups were trained on an animal treadmill for 60 min/day five times per week for eight weeks.

Findings/Results: The results revealed a significant increase in FAT/CD36, PTP1B, significantly decreased HNF4α genes expression, increase in LDL and cholesterol in the aged group compared to the young control. Compared to those in the young control group, no significant changes in HDL and TG amounts in the aged control were observed. Moreover, compared to the young control, the aged group showed liver histological changes such as fibrosis and mild or grade 1 steatohepatitis. Moderate aerobic exercise and curcumin alone or in combination completely masked this effect.

Conclusion and implications: The findings revealed dyslipidemia and liver steatosis related to aging might be partly associated with changes in hepatic transcriptional factors which can be mitigated via moderate aerobic exercise and curcumin.




Keywords: Aerobic exercise; Curcumin; FAT/CD36; PTP1B; Rat; Steatosis.

Full Text:



Pan M, Deng Y, Zheng C, Nie H, Tang K, Zhang Y, et al. The effects of Qigong exercises on blood lipid profiles of middle-aged and elderly individuals: a systematic review and network meta-analysis. Eur J Integr Med. 2019;30:100950.

DOI: 10.1016/j.eujim.2019.100950.

Hohn A, Grune T. Lipofuscin: formation, effects and role of macroautophagy. Redox Biol. 2013;1(1):140-144.

DOI: 10.1016/j.redox.2013.01.006.

Tsuruta G, Tanaka M, Hongo M, Komatsu A, Horiuchi K, Hamamoto, et al. Nonalcoholic fatty liver disease in Japanese junior high school students: its prevalence and relationship to lifestyle habits. J Gastroenterol. 2010;45(6):666-672.

DOI: 10.1007/s00535-009-0198-4.

Choi SS, Diehl AM. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr Opin Lipidol. 2008;19(3):295-300.

DOI: 10.1097/MOL.0b013e3282ff5e55.

Roth GA, Huffman MD, Moran AE, Feigin V, Mensah GA, Naghavi M, et al. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation. 2015;132(17):1667-1678.

DOI: 10.1161/CIRCULATIONAHA.114.008720.

Gliemann L, Nyberg M, Hellsten Y. Effects of exercise training and resveratrol on vascular health in aging. Free Radic Biol Med. 2016;98:165-176.

DOI: 10.1016/j.freeradbiomed.2016.03.037.

Shirpoor A, Heshmati E, Kheradmand F, Gharalari FH, Chodari L, Naderi R, et al. Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: rescue effect of ginger extract. Biomed Pharmacother. 2018;105:144-150.

DOI: 10.1016/j.biopha.2018.05.121.

Karagianni P, Talianidis I. Transcription factor networks regulating hepatic fatty acid metabolism. Biochim Biophys Acta. 2015;1851(1):2-8.

DOI: 10.1016/j.bbalip.2014.05.001.

Bakke J, Haj FG. Protein-tyrosine phosphatase 1B substrates and metabolic regulation. Semin Cell Dev Biol. 2015;37:58-65.

DOI: 10.1016/j.semcdb.2014.09.020.

Garbacz WG, Lu P, Miller TM, Poloyac SM, Eyre NS, Mayrhofer G, et al. Hepatic overexpression of CD36 improves glycogen homeostasis and attenuates high-fat diet-induced hepatic steatosis and insulin resistance. Mol Cell Biol. 2016;36(21):2715-2727.

DOI: 10.1128/MCB.00138-16.

Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol. 2012;39(3):283-299.

DOI: 10.1111/j.1440-1681.2011.05648.x.

Wang R, Tian H, Guo D, Tian Q, Yao T, Kong X. Impacts of exercise intervention on various diseases in rats. J Sport Health Sci. 2020;9(3):211-217.

DOI: 10.1016/j.jshs.2019.09.008.

Seif el-Din SH, El-Lakkany NM, El-Naggar AA, Hammam OA, Abd El-Latif HA, Ain-Shoka AA, et al. Effects of rosuvastatin and/or B-carotene on non-alcoholic fatty liver in rats. Res Pharm Sci. 2015;10(4):275-287.

DOI: 10.1111/j.1572-0241.1999.01377.x.

Ashcroft T, Simpson JM, Timbrell V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 1988;41(4):467-470.

DOI: 10.1136/jcp.41.4.467.

de Piano A, de Mello MT, Sanches PL, da Silva PL, Campos RM, Carnier J, et al. Long-term effects of aerobic plus resistance training on the adipokines and neuropeptides in nonalcoholic fatty liver disease obese adolescents. Eur J Gastroenterol Hepatol. 2012;24(11):1313-1324.

DOI: 10.1097/MEG.0b013e32835793ac.

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(4):1105-1112.

DOI: 10.1002/hep.23129.

Kujala UM, Vaara JP, Kainulainen H, Vasankari T, Vaara E, Kyrolainen H. Associations of aerobic fitness and maximal muscular strength with metabolites in young men. JAMA Netw Open. 2019;2(8):e198265.

DOI: 10.1001/jamanetworkopen.2019.8265.

Khaoshbaten M, Gholami N, Sokhtehzari S, Monazami AH, Nejad MR. The effect of an aerobic exercise on serum level of liver enzymes and liver echogenicity in patients with non-alcoholic fatty liver disease. Gastroenterol Hepatol Bed Bench. 2013;6(Suppl 1):S112-S116.

Ghamarchehreh ME, Shamsoddini A, Alavian SM. Investigating the impact of eight weeks of aerobic and resistance training on blood lipid profile in elderly with non-alcoholic fatty liver disease: a randomized clinical trial. Gastroenterol Hepatol Bed Bench. 2019;12(3):190-196.

Bae JC, Suh S, Park SE, Rhee EJ, Park CY, Oh KW, et al. Regular exercise is associated with a reduction in the risk of NAFLD and decreased liver enzymes in individuals with NAFLD independent of obesity in Korean adults. PloS One. 2012;7(10):e46819,1-7.

DOI: 10.1371/journal.pone.0046819.

Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998;114(4):842-845.

DOI: 10.1016/s0016-5085(98)70599-2.

Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10(6):330-344.

DOI: 10.1038/nrgastro.2013.41.

Larter CZ, Chitturi S, Heydet D, Farrell GC. A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol. 2010;25(4):672-690.

DOI: 10.1111/j.1440-1746.2010.06253.x.

Kim IH, Kisseleva T, Brenner DA. Aging and liver disease. Curr Opin Gastroenterol. 2015;31(3):184-191.

DOI: 10.1097/MOG.0000000000000176.

Gomez-Cabrera MC, Domenech E, Viña J. Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med. 2008;44(2):126-131.

DOI: 10.1016/j.freeradbiomed.2007.02.001.

Whitsett M, VanWagner LB. Physical activity as a treatment of non-alcoholic fatty liver disease: a systematic review. World J Hepatol. 2015;7(16):2041-2052.

DOI: 10.4254/wjh.v7.i16.2041.

Sahebkar A. A systematic review and meta-analysis of randomized controlled trials investigating the effects of curcumin on blood lipid levels. Clin Nutr. 2014;33(3):406-414.

DOI: 10.1016/j.clnu.2013.09.012.

Baum L, Cheung SK, Mok VC, Lam LC, Leung VP, Hui E, et al. Curcumin effects on blood lipid profile in a 6-month human study. Pharmacol Res. 2007;56(6):509-514. DOI: 10.1016/j.phrs.2007.09.013.

Afrin R, Arumugam S, Rahman A, Wahed MI, Karuppagounder V, Harima M, et al. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-kappaB translocation. Int Immunopharmacol. 2017;44:174-182.

DOI: 10.1016/j.intimp.2017.01.016.

Farzaei MH, Zobeiri M, Parvizi F, El-Senduny FF, Marmouzi I, Coy-Barrera E, et al. Curcumin in liver diseases: a systematic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients. 2018;10(7):855-883.

DOI: 10.3390/nu10070855.

Pohl J, Ring A, Korkmaz U, Ehehalt R, Stremmel W. FAT/CD36-mediated long-chain fatty acid uptake in adipocytes requires plasma membrane rafts. Mol Biol Cell. 2005;16(1):24-31.

DOI: 10.1091/mbc.e04-07-0616.

El-Lakkany NM, Seif el-Din SH, Abdel-Aal Sabra AN, Hammam OA, Abd El-Latif FA. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver. Res Pharm Sci. 2016;11(5):374-382

DOI: 10.4103/1735-5362.192487

Krammer J, Digel M, Ehehalt F, Stremmel W, Fullekrug J, Ehehalt R. Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells. Int J Med Sci. 2011;8(7):599-614. DOI: 10.7150/ijms.8.599.

Zhang W, Chen R, Yang T, Xu N, Chen J, Gao Y, et al. Fatty acid transporting proteins: roles in brain development, aging, and stroke. Prostaglandins Leukot Essent Fatty Acids. 2018;136:35-45.

DOI: 10.1016/j.plefa.2017.04.004.

Qin B, Anderson RA, Kuzuya T, Kitaura Y, Shimomura Y. Multiple factors and pathways involved in hepatic very low density lipoprotein-apoB100 overproduction in Otsuka Long-Evans Tokushima Fatty rats. Atherosclerosis. 2012;222(2):409-416.

DOI: 10.1016/j.atherosclerosis.2012.03.033.

Rondinone CM, Trevillyan JM, Clampit J, Gum RJ, Berg C, Kroeger P, et al. Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis. Diabetes. 2002;51(8):2405-2411.

DOI: 10.2337/diabetes.51.8.2405.


  • There are currently no refbacks.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.