Horm Metab Res 2009; 41(4): 287-293
DOI: 10.1055/s-0028-1102937
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Effects of Exercise Training on Hepatic Microsomal Triglyceride Transfer Protein Content in Rats

N. A. Chapados 1 , M. Seelaender 2 , E. Levy 3 , J-M. Lavoie 1
  • 1Department of Kinesiology, University of Montreal, Montreal, Canada
  • 2Molecular Biology of the Cell Group, Institute of Biomedical Sciences, University of São Paulo, Brazil
  • 3Research Center, Sainte-Justine Hospital and Department of Nutrition, University of Montreal, Montreal, Canada
Further Information

Publication History

received 05.08.2008

accepted 15.10.2008

Publication Date:
20 November 2008 (online)

Abstract

Microsomal triglyceride transfer protein (MTP) is a protein that exerts a central regulatory role in very-low-density lipoprotein (VLDL) assembly and secretion. The purpose of the study was to investigate the effects of an exercise-training program on hepatic content of MTP and its relation to hepatic VLDL-triglyceride (VLDL-TG) production in response to lipid infusion. Female rats either fed a standard (SD) or an obesity-induced high-fat (HF; 43% as energy) diet for 8 weeks were subdivided into sedentary (Sed) and trained (Tr) groups. Exercise training consisted of continuous running on a motor-driven rodent treadmill 5 times/week for 8 weeks. At the end of this period, all rats in the fasted state were intravenously infused with a 20% solution of Intralipid for 3 h followed by an injection of Triton WR1339 to block lipoprotein lipase. An additional control group consisting of Sed rats fed the SD diet was infused with saline (0.9% NaCl). Plasma TG accumulation was thereafter measured during 90 min to estimate VLDL-TG production. Under HF diet, hepatic MTP content and plasma TG accumulation after Triton blockade (thus reflecting VLDL-TG synthesis and secretion) were not changed in Sed rats, whereas liver TG content was highly increased (∼90%; p<0.01). On the other hand, training reduced liver MTP protein content in both SD (−18%) and HF (–23%) fed rats (p<0.05). Plasma VLDL-TG accumulation was also lower (p<0.05) in Tr than in Sed rats fed the HF diet. This effect was not observed in SD fed rats. Furthermore, the exercise training-induced decrease in VLDL-TG production in HF rats was associated with a decrease in liver TG levels. It is concluded that in addition to a reduction in liver TG content, exercise training reduces VLDL synthesis and/or secretion in HF fed rats probably via MTP regulation.

References

  • 1 Formiguera X, Canton A. Obesity: epidemiology and clinical aspects.  Best Pract Res Clin Gastroenterol. 2004;  18 1125-1146
  • 2 Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.  JAMA. 2003;  289 76-79
  • 3 Eckel RH, Krauss RM. American Heart Association call to action: obesity as a major risk factor for coronary heart disease.  Circulation. 1998;  97 2099-2100
  • 4 Hu FB. Sedentary lifestyle and risk of obesity and type 2 diabetes.  Lipids. 2003;  38 103-108
  • 5 Festi D, Colecchia A, Sacco T, Bondi M, Roda E, Marchesini G. Hepatic steatosis in obese patients: clinical aspects and prognostic significance.  Obes Rev. 2004;  5 27-42
  • 6 Gauthier MS, Favier R, Lavoie JM. Time course of the development of non-alcoholic hepatic steatosis in response to high-fat diet-induced obesity in rats.  Br J Nutr. 2006;  95 273-281
  • 7 Collin P, Chapados N, Dufresne E, Corriveau P, Imbeault P, Lavoie JM. Time course of changes in vitro lipolysis of intra-abdominal fat depots in relation to high-fat diet-induced hepatic steatosis in rats.  Br J Nutr. 2006;  96 268-275
  • 8 Kotronen A, Seppala-Lindroos A, Bergholm R, Yki-Jarvinen H. Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome.  Diabetologia. 2008;  51 130-138
  • 9 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 1343-1351
  • 10 Pessayre D. Role of mitochondria in non-alcoholic fatty liver disease.  J Gastroenterol Hepatol. 2007;  22 S20-S27
  • 11 Wei Y, Rector RS, Thyfault JP, Ibdah JA. Nonalcoholic fatty liver disease and mitochondrial dysfunction.  World J Gastroenterol. 2008;  14 193-199
  • 12 Angulo P. Nonalcoholic fatty liver disease.  N Engl J Med. 2002;  346 1221-1231
  • 13 Tarugi P, Lonardo A, Ballarini G, Grisendi A, Pulvirenti M, Bagni A, Calandra S. Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B.  Gastroenterology. 1996;  111 1125-1133
  • 14 Suzuki A, Lindor K, St Saver J, Lymp J, Mendes F, Muto A, Okada T, Angulo P. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.  J Hepatol. 2005;  43 1060-1066
  • 15 Rector RS, Thyfault JP, Morris RT, Laye MJ, Borengasser SJ, Booth FW, Ibdah JA. Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.  Am J Physiol Gastrointest Liver Physiol. 2008;  294(3) G619-G626
  • 16 Gauthier MS, Couturier K, Charbonneau A, Lavoie JM. Effects of introducing physical training in the course of a 16-week high-fat diet regimen on hepatic steatosis, adipose tissue fat accumulation, and plasma lipid profile.  Int J Obes Relat Metab Disord. 2004;  28 1064-1071
  • 17 Gauthier MS, Couturier K, Latour JG, Lavoie JM. Concurrent exercise prevents high-fat-diet-induced macrovesicular hepatic steatosis.  J Appl Physiol. 2003;  94 2127-2134
  • 18 Chapados N, Collin P, Imbeault P, Corriveau P, Lavoie JM. Exercise training decreases in vitro stimulated lipolysis in a visceral (mesenteric) but not in the retroperitoneal fat depot of high-fat-fed rats.  Br J Nutr. 2008;  100 518-525
  • 19 Griffiths MA, Baker DH, Novakofski JE, Ji LL. Effects of exercise training on diet-induced lipogenic enzymes and body composition in rats.  J Am Coll Nutr. 1993;  12 155-161
  • 20 Tsekouras YE, Magkos F, Kellas Y, Basioukas KN, Kavouras SA, Sidossis L. High-intensity interval aerobic training reduces hepatic very low density lipoprotein-triglyceride secretion rate in men.  Am J Physiol Endocrinol. 2008;  295(4) E851-E858
  • 21 Gibbons GF, Wiggins D, Brown AM, Hebbachi AM. Synthesis and function of hepatic very-low-density lipoprotein.  Biochem Soc Trans. 2004;  32 59-64
  • 22 Bartels ED, Lauritsen M, Nielsen LB. Hepatic expression of microsomal triglyceride transfer protein and in vivo secretion of triglyceride-rich lipoproteins are increased in obese diabetic mice.  Diabetes. 2002;  51 1233-1239
  • 23 Tietge UJF, Bakillah A, Maugeais C, Tsukamoto K, Hussain M, Rader DJ. Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B.  J Lipid Res. 1999;  40 2134-2139
  • 24 Raabe M, Veniant MM, Sullivan MA, Zlot CH, Bjorkegren J, Nielsen LB, Wong JS, Hamilton RL, Young SG. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice.  J Clin Invest. 1999;  103 1287-1298
  • 25 Gambino R, Cassader M, Pagano G, Durazzo M, Musso G. Polymorphism in microsomal triglyceride transfer protein: a link between liver disease and atherogenic postprandial lipid profile in NASH?.  Hepatology. 2007;  45 1097-1107
  • 26 Letteron P, Sutton A, Mansouri A, Fromenty B, Pessayre D. Inhibition of microsomal triglyceride transfer protein: another mechanism for drug-induced steatosis in mice.  Hepatology. 2003;  38 133-140
  • 27 Zhang Y-L, Hernandez-Ono A, Ko C, Yasunaga K, Huang L-S, Ginsberg HN. Regulation of hepatic apolipoprotein B-lipoprotein assembly and secretion by the availability of fatty acids: I. Differential response to the delivery of fatty acids via albumin or remnant-like emulsion particles.  J Biol Chem. 2004;  279 19362-19374
  • 28 Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans.  J Clin Invest. 1995;  95 158-166
  • 29 Tarugi P, Averna M, Leo E Di, Cefalu AB, Noto D, Magnolo L, Cattin L, Bertolini S, Calandra S. Molecular diagnosis of hypobetalipoproteinemia: an ENID review.  Atherosclerosis. 2007;  195 e19-e27
  • 30 Lira FS, Tavares FL, Yamashita AS, Koyama CH, Alves MJ, Caperuto EC, Batista Jr ML, Seelaender M. Effect of endurance training upon lipid metabolism in the liver of cachectic tumour-bearing rats.  Cell Biochem Funct. 2008;  26 701-708
  • 31 den Boer M, Voshol PJ, Kuipers F, Havekes LM, Romijn JA. Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models.  Arterioscler Thromb Vasc Biol. 2004;  24 644-649
  • 32 Magkos F, Wright DC, Patterson BW, Mohammed BS, Mittendorfer B. Lipid metabolism response to a single, prolonged bout of endurance exercise in healthy young men.  Am J Physiol Endocrinol Metab. 2006;  290 E355-E362
  • 33 Sparks JD, Sparks CE. Insulin modulation of hepatic synthesis and secretion of apolipoprotein B by rat hepatocytes.  J Biol Chem. 1990;  265 8854-8862
  • 34 Lin MC, Gordon D, Wetterau JR. Microsomal triglyceride transfer protein (MTP) regulation in HepG2 cells: insulin negatively regulates MTP gene expression.  J Lipid Res. 1995;  36 1073-1081
  • 35 Zoltowska M, Ziv E, Delvin E, Lambert M, Seidman E, Levy E. Both insulin resistance and diabetes in Psammomys obesus upregulate the hepatic machinery involved in intracellular VLDL assembly.  Arterioscler Thromb Vasc Biol. 2004;  24 118-123
  • 36 Lehmann R, Vokac A, Niedermann K, Agosti K, Spinas GA. Loss of abdominal fat and improvement of the cardiovascular risk profile by regular moderate exercise training in patients with NIDDM.  Diabetologia. 1995;  38 1313-1319
  • 37 Mourier A, Gautier JF, Kerviler E De, Bigard AX, Villette JM, Garnier JP, Duvallet A, Guezennec CY, Cathelineau G. Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM. Effects of branched-chain amino acid supplements.  Diabetes Care. 1997;  20 385-391
  • 38 Gibbons GF, Islam K, Pease RJ. Mobilisation of triacylglycerol stores.  Biochim Biophys Acta. 2000;  1483 37-57
  • 39 Chandler CE, Wilder DE, Pettini JL, Savoy YE, Petras SF, Chang G, Vincent J, Harwood HJ. CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans.  J Lipid Res. 2003;  44 1887-1901
  • 40 Liao W, Hui TY, Young SG, Davis RA. Blocking microsomal triglyceride transfer protein interferes with apoB secretion without causing retention or stress in the ER.  J Lipid Res. 2003;  44 978-985

Correspondence

N. A. Chapados

Department of Kinesiology

University of Montreal

C.P. 6128, Succ. Centre-ville

Montréal (Québec)

Canada H3C 3J7

Phone: +1/514/343 61 11 (4867)

Fax: +1/514/343 21 81

Email: natalie.chapados@umontreal.ca

    >