Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig
Tóm tắt
Betaine affects fat metabolism in animals, but the specific mechanism is still not clear. The purpose of this study was to investigate possible mechanisms of betaine in altering lipid metabolism in muscle tissue in finishing pigs. A total of 120 crossbred gilts (Landrace × Yorkshire × Duroc) with an average initial body weight of 70.1 kg were randomly allotted to three dietary treatments. The treatments included a corn–soybean meal basal diet supplemented with 0, 1250 or 2500 mg/kg betaine. The feeding experiment lasted 42 d. Betaine addition to the diet significantly increased the concentration of free fatty acids (FFA) in muscle (P < 0.05). Furthermore, the levels of serum cholesterol and high-density lipoprotein cholesterol were decreased (P < 0.05) and total cholesterol content was increased in muscle (P < 0.05) of betaine fed pigs. Experiments on genes involved in fatty acid transport showed that betaine increased expression of lipoprotein lipase(LPL), fatty acid translocase/cluster of differentiation (FAT/CD36), fatty acid binding protein (FABP3) and fatty acid transport protein (FATP1) (P < 0.05). The abundance of fatty acid transport protein and fatty acid binding protein were also increased by betaine (P < 0.05). As for the key factors involved in fatty acid oxidation, although betaine supplementation didn’t affect the level of carnitine and malonyl-CoA, betaine increased mRNA and protein abundance of carnitine palmitransferase-1(CPT1) and phosphorylated-AMPK (P < 0.05). The results suggested that betaine may promoted muscle fatty acid uptake via up-regulating the genes related to fatty acid transporter including FAT/CD36, FATP1 and FABP3. On the other hand, betaine activated AMPK and up-regulated genes related to fatty acid oxidation including PPARα and CPT1. The underlying mechanism regulating fatty acid metabolism in pigs supplemented with betaine is associated with the up-regulation of genes involved in fatty acid transport and fatty acid oxidation.
Tài liệu tham khảo
Eklund M, Bauer E, Wamatu J, Mosenthin R. Potential nutritional and physiological functions of betaine in livestock. Nutr Res Rev. 2005;18(01):31–48.
Craig SAS. Betaine in human nutrition. Am J Clin Nutr. 2004;80(3):539–49.
Wray-Cahen D, Fernández-Fígares I, Virtanen E, Steele NC, Caperna TJ. Betaine improves growth, but does not induce whole body or hepatic palmitate oxidation in swine (Sus Scrofa Domestica). Comp Biochem Physiol A Mol Integr Physiol. 2004;137(1):131–40.
Fernández-Fígares I, Wray-Cahen D, Steele NC, Campbell RG, Hall DD, Virtanen E, et al. Effect of dietary betaine on nutrient utilization and partitioning in the young growing feed-restricted pig. J Anim Sci. 2002;80(2):421–8.
Schrama JW, Heetkamp MJW, Simmins PH, Gerrits WJJ. Dietary betaine supplementation affects energy metabolism of pigs. J Anim Sci. 2003;81(5):1202–9.
Wang YZ, Xu ZR, Feng J. The effect of betaine and DL-methionine on growth performance and carcass characteristics in meat ducks. Anim Feed Sci Technol. 2004;116(1):151–9.
Feng J, Liu X, Wang YZ, Xu ZR. Effects of betaine on performance, carcass characteristics and hepatic betaine-homocysteine methyltransferase activity in finishing barrows. Asian-Australas J Anim Sci. 2006;19(3):402.
Huang QC, Xu ZR, Han XY, Li WF. Changes in hormones, growth factor and lipid metabolism in finishing pigs fed betaine. Livest Sci. 2006;105(1):78–85.
Huang QC, Xu ZR, Han XY, Li WF. Effect of betaine on growth hormone pulsatile secretion and serum metabolites in finishing pigs. J Anim Physiol Anim Nutr (Berl). 2007;91(3–4):85–90.
Nakev J, Popova T, Vasileva V. Influence of dietary betaine supplementation on the growth performance and carcass characteristics in male and female growing-finishing pigs. Bulg J Agric Sci. 2009;15(3):263–8.
Pekkinen J, Olli K, Huotari A, Tiihonen K, Keski-Rahkonen P, Lehtonen M, et al. Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach. Mol Nutr Food Res. 2013;57(11):1959–68.
Xu L, Huang D, Hu Q, Wu J, Wang Y, Feng J. Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet. Br J Nutr. 2015;113(12):1835–43.
Zhang W, Wang L, Wang L, Li X, Zhang H, Luo L, et al. Betaine protects against high-fat-diet-induced liver injury by inhibition of high-mobility group box 1 and toll-like receptor 4 expression in rats. Dig Dis Sci. 2013;58(11):3198–206.
Deminice R, Da Silva RP, Lamarre SG, Kelly KB, Jacobs RL, Brosnan ME, et al. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism. Amino Acids. 2015;47(4):839–46.
Huang QC, Han XY, Xu ZR, Yang XY, Chen T, Zheng XT. Betaine suppresses carnitine palmitoyltransferase I in skeletal muscle but not in liver of finishing pigs. Livest Sci. 2009;126(1):130–5.
Martins JM, Neves JA, Freitas A, Tirapicos JL. Effect of long-term betaine supplementation on chemical and physical characteristics of three muscles from the Alentejano pig. J Sci Food Agric. 2012;92(10):2122–7.
Madeira MS, Rolo EA, Alfaia CM, Pires VR, Luxton R, Doran O, et al. Influence of betaine and arginine supplementation of reduced protein diets on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of cross-bred pigs. Br J Nutr. 2016;115(06):937–50.
National Research Council. Nutrient requirements of swine: eleventh revised edition. Washington, D.C.: The National Academies Press; 2012.
Association of Official Analytical Chemists (AOAC). Van Nostrand's Encyclopedia of Chemistry. Hoboken: John Wiley & Sons, Inc. 2005.
Zeng T, Xie K, Zhang C, Yu L, Zhu Z. Determination the level of triglycerides in liver with chloroform/ methanol homogenate. J Hyg Res. 2008;37(5):550–1. (in Chinese)
Nygard A-B, Jørgensen CB, Cirera S, Fredholm M. Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR. BMC Mol Biol. 2007;8(1):67.
Erkens T, Van Poucke M, Vandesompele J, Goossens K, Van Zeveren A, Peelman LJ. Development of a new set of reference genes for normalization of real-time PT-PCR data of porcine backfat and longissimus dorsi muscle, and evaluation with PPARGC1A. BMC Biotechnol. 2006;6:41.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–8.
Lopaschuk GD, Ussher JR, Folmes CDL, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010;90(1):207–58.
Kelley DE, Goodpaster B, Wing RR, Simoneau J-A. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol-Endoc M. 1999;277(6):E1130–41.
Clarke SD. Regulation of fatty acid synthase gene expression: an approach for reducing fat accumulation. J Anim Sci. 1993;71(7):1957.
Christensen K. In vitro studies on the synthesis of intramuscular fat in the longissimus dorsh muscle of pigs. Livest Prod Sci. 1975;2(1):59–68.
Yang HS, Lee JI, Joo ST, Park GB. Effects of dietary glycine betaine on growth and pork quality of finishing pigs. Asian-australas J Anim Sci. 2009;22(5):706–11.
Fernández-Fígares I, Lachica M, Martín A, Nieto R, Gonzalez-valero L, Rodriguez-Lopez JM, et al. Impact of dietary betaine and conjugated linoleic acid on insulin sensitivity, protein and fat metabolism of obese pigs. Animal. 2012;6(07):1058–67.
Nickerson JG, Alkhateeb H, Benton CR, Lally J, Nickerson J, Han XX, et al. Greater transport efficiencies of the membrane fatty acid transporters FAT/CD36 and FATP4 compared with FABPpm and FATP1 and differential effects on fatty acid esterification and oxidation in rat skeletal muscle. J Biol Chem. 2009;284(24):16522–30.
Sebastián D, Guitart M, García-Martínez C, Mauvazin C, Orellana-Gavalda JM, Serra D, et al. Novel role of FATP1 in mitochondrial fatty acid oxidation in skeletal muscle cells. J Lipid Res. 2009;50(9):1789–99.
Ibrahimi A, Bonen A, Blinn WD, Hajri T, Li X, Zhong K, et al. Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscle, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin. J Biol Chem. 1999;274(38):26761–6.
Hertzel AV, Bernlohr DA. The mammalian fatty acid-binding protein multigene family: molecular and genetic insights into function. Trends Endocrinol Metab. 2000;11(5):175–80.
Glatz JFC, Schaap FG, Binas B, Bonen A, Van Der Vusse GJ, Luiken JJFP. Cytoplasmic fatty acid-binding protein facilitates fatty acid utilization by skeletal muscle. Acta Physiol Scand. 2003;178(4):367–71.
Cho KH, Kim MJ, Jeon GJ, Chung HY. Association of genetic variants for FABP3 gene with back fat thickness and intramuscular fat content in pig. Mol Biol Rep. 2011;38(3):2161–6.
Gerbens F, Verburg FJ, Van Moerkerk HTB, Engel B, Buist W, Veerkamp JH, et al. Associations of heart and adipocyte fatty acid-binding protein gene expression with intramuscular fat content in pigs. J Anim Sci. 2001;79(2):347–54.
Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, Kako Y, et al. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. J Clin Invest. 2003;111(3):419–26.
Walczak R, Tontonoz P. PPARadigms and PPARadoxes: expanding roles for PPARγ in the control of lipid metabolism. J Lipid Res. 2002;43(2):177–86.
Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000;14(11):1293–307.
Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. PPAR [gamma] signaling and metabolism: the good, the bad and the future. Nat Med. 2013;99(5):557–66.
Albuquerque A, Neves JA, Redondeiro M, Laranjo M, Felix MR, Freitas A, et al. Long term betaine supplementation regulates genes involved in lipid and cholesterol metabolism of two muscles from an obese pig breed. Meat Sci. 2017;124:25–33.
Saha AK, Ruderman NB. Malonyl-CoA and AMP-activated protein kinase: an expanding partnership. Mol Cell Biochem. 2003;253(1):65–70.
Xue B, Kahn BB. AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol Lond. 2006;574(1):73–83.
Cai D, Wang J, Jia Y, Liu H, Yuan M, Dong H, et al. Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms. Biochim Biophys Acta. 2016;1861(1):41–50.
Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13(4):251–62.
Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS, et al. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARα and PGC-1. Biochem Biophys Res Commun. 2006;340(1):291–5.
Ferré P. The biology of peroxisome proliferator-activated receptors. Diabetes. 2004;53(suppl 1):S43–50.
Matthews JO, Southern LL, Higbie AD, Persica MA, Bidner TD. Effects of betaine on growth, carcass characteristics, pork quality, and plasma metabolites of finishing pigs. J Anim Sci. 2001;79(3):722–8.
Martins JM, Neves JA, Freitas A, Tirapicos JL. Research article Betaine supplementation affects the cholesterol but not the lipid profile of pigs. Eur J Lipid Sci Technol. 2010;112:295–303.