Isoleucine and aerobic training regulated the hepatic metabolism in obese mice.
Subject Areas : Exercise Physiology and Performance
Farzad Forootan
1
(Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.)
Fatemeh Hajibabaie
2
(Department of Biology, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.)
Zahra Ahmadi
3
(Department of Physiology, Medicinal Plants Research Center, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran.)
Keywords: liver, isoleucine, Aerobic exercise, Ppar-γ, Pgc1, Ucp2,
Abstract :
Background: Obesity harmfully affects all physiological functions of the body and public health. Valine(Valine) are crucial amino acids, including leucine, isoleucine, and valine. Isoleucine could influence protein metabolism, apoptosis, regeneration of hepatocytes, and insulin resistance. Previous studies demonstrated that elevated circulating isoleucine are strongly associated with metabolic disorders, such as obesity, metabolic syndrome, and type 2 diabetes mellitus. This study examines the effect of Isoleucine supplements on hepatic lipogenesis and obesity following an acute bout of exercise in adult mice.Methods: Thirty male mice of type C57BL/6 were distributed randomly into five groups: Regular diet group, High-fat diet group, Exercise group, Regular diet+20% Isoleucine diet group, and 20% Isoleucine diet+Exercise group. Next, each group was sacrificed and then, the liver was collected; Real-time qPCR investigated the expression of mRNA levels.Results: Our data indicated that the Exercise group, 20%VALINE, and 20% VALINE+Exercise groups, significantly amplified the levels of Ucp2, Ppar-γ, Ppar-α, and Pgc1-α mRNA compared to the control group. In contrast, the expression level of Ppar-α in the high-fat diet group compared to the control group was decreased.Conclusion: Interestingly, a high-fat diet was due to down-regulated expression levels of Pgc1-α, Ppar-γ, and Ucp2 in the liver, but Ppar-α increased.
1-Oh KS, Kim M, Lee J, Kim MJ, Nam YS, Ham JE, et al. Liver PPARalpha and UCP2 are involved in the regulation of obesity and lipid metabolism by swim training in genetically obese db/db mice. Biochem Biophys Res Commun. 2006;345(3):1232-9. DOI: 10.1016/j.bbrc.2006.04.182
2-King GA, Fitzhugh EC, Bassett DR, Jr., McLaughlin JE, Strath SJ, Swartz AM, et al. Relationship of leisure-time physical activity and occupational activity to the prevalence of obesity. Int J Obes Relat Metab Disord. 2001;25(5):606-12. DOI: 10.1038/sj.ijo.0801583
3-Wier LT, Ayers GW, Jackson AS, Rossum AC, Poston WS, Foreyt JP. Determining the amount of physical activity needed for long-term weight control. Int J Obes Relat Metab Disord. 2001;25(5):613-21. DOI: 10.1038/sj.ijo.0801586
4-Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98-107. DOI: 10.1038/nri2925
5-Lackey DE, Olefsky JM. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol. 2016;12(1):15-28. DOI: 10.1038/nrendo.2015.189
6-Lee YS, Wollam J, Olefsky JM. An Integrated View of Immunometabolism. Cell. 2018;172(1-2):22-40. DOI: 10.1016/j.cell.2017.12.025
7-Ying W, Fu W, Lee YS, Olefsky JM. The role of macrophages in obesity-associated islet inflammation and beta-cell abnormalities. Nat Rev Endocrinol. 2020;16(2):81-90. DOI: 10.1038/s41574-019-0286-3
8-Abedpoor N, Taghian F, Ghaedi K, Niktab I, Safaeinejad Z, Rabiee F, et al. PPARgamma/Pgc-1alpha-Fndc5 pathway up-regulation in gastrocnemius and heart muscle of exercised, branched chain amino acid diet fed mice. Nutr Metab (Lond). 2018;15:59. DOI: 10.1186/s12986-018-0298-3
9-Harris RA, Joshi M, Jeoung NH, Obayashi M. Overview of the molecular and biochemical basis of branched-chain amino acid catabolism. J Nutr. 2005;135(6 Suppl):1527S-30S. DOI: 10.1093/jn/135.6.1527S
10-Nie C, He T, Zhang W, Zhang G, Ma X. Branched Chain Amino Acids: Beyond Nutrition Metabolism. Int J Mol Sci. 2018;19(4). DOI: 10.3390/ijms19040954
11-Saad MJ, Santos A, Prada PO. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance. Physiology (Bethesda). 2016;31(4):283-93. DOI: 10.1152/physiol.00041.2015
12-Reilly SM, Saltiel AR. Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol. 2017;13(11):633-43. DOI: 10.1038/nrendo.2017.90
13-D'Antona G, Ragni M, Cardile A, Tedesco L, Dossena M, Bruttini F, et al. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab. 2010;12(4):362-72. DOI: 10.1016/j.cmet.2010.08.016
14-Tajiri K, Shimizu Y. Valinein liver diseases. World J Gastroenterol. 2013;19(43):7620-9. DOI: 10.3748/wjg.v19.i43.7620
15-Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB, et al. Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature. 2000;406(6794):415-8. DOI: 10.1038/35019082
16-Arakawa M, Masaki T, Nishimura J, Seike M, Yoshimatsu H. The effects of branched-chain amino acid granules on the accumulation of tissue triglycerides and uncoupling proteins in diet-induced obese mice. Endocr J. 2011;58(3):161-70. DOI: 10.1507/endocrj.k10e-221
17-Liang CP, Tall AR. Transcriptional profiling reveals global defects in energy metabolism, lipoprotein, and bile acid synthesis and transport with reversal by leptin treatment in ob/ob mouse liver. J Biol Chem. 2001;276(52):49066-76. DOI: 10.1074/jbc.M107250200
18-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(5):1343-51. DOI: 10.1172/JCI23621
19-Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest. 2008;118(3):829-38. DOI: 10.1172/JCI34275
20-O'Donnell JS, Massi D, Teng MWL, Mandala M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol. 2018;48:91-103. DOI: 10.1016/j.semcancer.2017.04.015
21-Dey N, De P, Leyland-Jones B. PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trials. Pharmacol Ther. 2017;175:91-106. DOI: 10.1016/j.pharmthera.2017.02.037
22-Marchesini G, Marzocchi R, Noia M, Bianchi G. Branched-chain amino acid supplementation in patients with liver diseases. J Nutr. 2005;135(6 Suppl):1596S-601S. DOI: 10.1093/jn/135.6.1596S
23-Casperson SL, Sheffield-Moore M, Hewlings SJ, Paddon-Jones D. Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein. Clin Nutr. 2012;31(4):512-9. DOI: 10.1016/j.clnu.2012.01.005
24-Ispoglou T, White H, Preston T, McElhone S, McKenna J, Hind K. Double-blind, placebo-controlled pilot trial of L-Leucine-enriched amino-acid mixtures on body composition and physical performance in men and women aged 65-75 years. Eur J Clin Nutr. 2016;70(2):182-8. DOI: 10.1038/ejcn.2015.91
25-Matsumoto T, Nakamura K, Matsumoto H, Sakai R, Kuwahara T, Kadota Y, et al. Bolus ingestion of individual Valinealters plasma amino acid profiles in young healthy men. Springerplus. 2014;3:35.
DOI: 10.1186/2193-1801-3-35
26-Mikulski T, Dabrowski J, Hilgier W, Ziemba A, Krzeminski K. Effects of supplementation with branched chain amino acids and ornithine aspartate on plasma ammonia and central fatigue during exercise in healthy men. Folia Neuropathol. 2015;53(4):377-86. DOI: 10.5114/fn.2015.56552
27-Zhang Y, Kobayashi H, Mawatari K, Sato J, Bajotto G, Kitaura Y, et al. Effects of branched-chain amino acid supplementation on plasma concentrations of free amino acids, insulin, and energy substrates in young men. J Nutr Sci Vitaminol (Tokyo). 2011;57(1):114-7. DOI: 10.3177/jnsv.57.114
28-Shimomura Y, Inaguma A, Watanabe S, Yamamoto Y, Muramatsu Y, Bajotto G, et al. Branched-chain amino acid supplementation before squat exercise and delayed-onset muscle soreness. Int J Sport Nutr Exerc Metab. 2010;20(3):236-44. DOI: 10.1123/ijsnem.20.3.236
29-Pitkanen HT, Oja SS, Rusko H, Nummela A, Komi PV, Saransaari P, et al. Leucine supplementation does not enhance acute strength or running performance but affects serum amino acid concentration. Amino Acids. 2003;25(1):85-94. DOI: 10.1007/s00726-002-0343-3
30-Cavallaro NL, Garry J, Shi X, Gerszten RE, Anderson EJ, Walford GA. A pilot, short-term dietary manipulation of branched chain amino acids has modest influence on fasting levels of branched chain amino acids. Food Nutr Res. 2016;60:28592. DOI: 10.3402/fnr.v60.28592
31-Guerre-Millo M, Rouault C, Poulain P, Andre J, Poitout V, Peters JM, et al. PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance. Diabetes. 2001;50(12):2809-14. DOI: 10.2337/diabetes.50.12.2809
32-Guerre-Millo M, Gervois P, Raspe E, Madsen L, Poulain P, Derudas B, et al. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000;275(22):16638-42. DOI: 10.1074/jbc.275.22.16638
33-Stienstra R, Mandard S, Patsouris D, Maass C, Kersten S, Muller M. Peroxisome proliferator-activated receptor alpha protects against obesity-induced hepatic inflammation. Endocrinology. 2007;148(6):2753-63. DOI: 10.1210/en.2007-0014
34-Knauf C, Rieusset J, Foretz M, Cani PD, Uldry M, Hosokawa M, et al. Peroxisome proliferator-activated receptor-alpha-null mice have increased white adipose tissue glucose utilization, GLUT4, and fat mass: Role in liver and brain. Endocrinology. 2006;147(9):4067-78. DOI: 10.1210/en.2005-1536