Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity

Nutrients

Volumn 7, Issue 2, 2015, Pages 1202-1216

  Dunlop, Kristyn ^a   Cedrone, Megan ^a   Staples, James F ^a   Regnault, Timothy R H ^a,b,c  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

^b LAWSON HEALTH RESEARCH INSTITUTE   (Canada)

^c CHILDREN S HEALTH RESEARCH INSTITUTE   (Canada)

Author keywords

Acylcarnitine; Fats; Hypoxia; Insulin sensitivity; IUGR; Mitochondria; Obese; Oxygen; Skeletal muscle; oxidation

Indexed keywords

3 PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE; ACYL COENZYME A; ADENOSINE TRIPHOSPHATE; DIACYLGLYCEROL; FATTY ACID; GLUCOSE TRANSPORTER 4; GLUTAMIC ACID; I KAPPA B; INSULIN RECEPTOR; INSULIN RECEPTOR SUBSTRATE; INSULIN RECEPTOR SUBSTRATE 1; MALIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE C; PYRUVIC ACID; ROTENONE; SERINE; STRESS ACTIVATED PROTEIN KINASE; SUCCINIC ACID; THREONINE; INSULIN;

DISEASE ASSOCIATION; DISEASE COURSE; ELECTRON TRANSPORT; ENERGY METABOLISM; EPIGENETICS; FATTY ACID OXIDATION; GLUCOSE TOLERANCE; GLUCOSE TRANSPORT; GLYCOLYSIS; HUMAN; HYPOXIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTRAUTERINE GROWTH RETARDATION; LOW BIRTH WEIGHT; METABOLIC DISORDER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUTRIENT; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; ADULT; AGING; DIET; FEMALE; FETUS DEVELOPMENT; GROWTH, DEVELOPMENT AND AGING; INFANT; MALE; MATERNAL NUTRITION; METABOLIC DISEASES; METABOLISM; MIDDLE AGED; NEWBORN; PATHOPHYSIOLOGY; PREGNANCY; RISK FACTOR;

ANIMALIA;

ADULT; AGING; DIET; FEMALE; FETAL DEVELOPMENT; FETAL GROWTH RETARDATION; HUMANS; INFANT; INFANT, LOW BIRTH WEIGHT; INFANT, NEWBORN; INSULIN; INSULIN RESISTANCE; MALE; METABOLIC DISEASES; MIDDLE AGED; MUSCLE, SKELETAL; PREGNANCY; PRENATAL NUTRITIONAL PHYSIOLOGICAL PHENOMENA; RISK FACTORS;

EID: 84923023892     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu7021202     Document Type: Review

References (78)

1. Osmond, C.; Barker, D.J. Fetal, infant and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women. Environ. Health Perspect.2000, 108, 545–553
2. Kind, K.L.; Clifton, P.M.; Grant, P.A.; Owens, P.C.; Sohlstrom, A.; Roberts, C.T.; Robinson, J.S.; Owens, J.A. Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig. Am. J. Physiol. Regul. Integr. Comp. Physiol.2003, 284, R140–R152
3. Leger, J.; Levy-Marchal, C.; Bloch, J.; Pinet, A.; Chevenne, D.; Porquet, D.; Collin, D.; Czernichow, P. Reduced final height and indications for insulin resistance in 20 year olds small for gestational age: Regional cohort study. BMJ 1997, 315, 341–347
4. Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z. The metabolic syndrome. Lancet2005, 365, 1415–1428
5. Barker, D.J. The developmental origins of insulin resistance. Horm. Res.2005, 64(Suppl. 3), 2–7
6. Pollack, R.N.; Divon, M.Y. Intrauterine growth retardation: Definition, classification and etiology. Clin. Obsetrics Gynecol.1992, 35, 99–107.
7. Bamberg, C.; Kalache, K.D. Prenatal diagnosis of fetal growth restriction. Semin. Fetal Neonatal Med.2004, 9, 387–394
8. Giussani, D.A.; Salinas, C.E.; Villena, M.; Blanco, C.E. The role of oxygen in prenatal growth: Studies in the chick embryo. J. Physiol.2007, 585, 911–917
9. Arbeille, P. Fetal arterial doppler-iugr and hypoxia. Eur. J. Obstetrics Gynecol. Reprod. Biol.1997, 75, 51–53
10. Baschat, A.A. Fetal responses to placental insufficiency: An update. BJOG Int. J. Obstetrics Gynaecol.2004, 111, 1031–1041
11. Rurak, D.W.; Richardson, B.S.; Patrick, J.E.; Carmichael, L.; Homan, J. Blood flow and oxygen delivery to fetal organs and tissues during sustained hypoxemia. Am. J. Physiol.1990, 258, 1116–1122
12. Dubiel, M.; Breborowicz, G.H.; Gudmundsson, S. Evaluation of fetal circulation redistribution in pregnancies with absent or reversed diastolic flow in the umbilical artery. Early Hum. Dev.2003, 71, 149–156
13. Dubiel, M.; Breborowicz, G.H.; Marsal, K.; Gudmundsson, S. Fetal adrenal and middle cerebral artery doppler velocimetry in high-risk pregnancy. Ultrasound Obstetrics Gynecol. 2000, 16, 414–418.
14. Salihagic-Kadic, A.; Medic, M.; Jugovic, D.; Kos, M.; Latin, V.; Kusan Jukic, M.; Arbeille, P. Fetal cerebrovascular response to chronic hypoxia—Implications for the prevention of brain damage. J. Mater. Fetal Neonatal Med. 2006, 19, 387–396.
15. Poudel, R.; McMillen, I.C.; Dunn, S.L.; Zhang, S.; Morrison, J.L. Impact of chronic hypoxemia on blood flow to the brain, heart and adrenal gland in the late gestation iugr sheep fetus. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014, doi:10.1152/ajpregu.00036.2014.
16. Jensen, C.B.; Martin-Gronert, M.S.; Storgaard, H.; Madsbad, S.; Vaag, A.; Ozanne, S.E. Altered pi3-kinase/akt signalling in skeletal muscle of young men with low birth weight. PLoS One 2008, 3, e3738, doi:10.1371/journal.pone.0003738
17. Jensen, C.B.; Storgaard, H.; Madsbad, S.; Richter, E.A.; Vaag, A.A. Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight. J. Clin. Endocrinol. Metab. 2007, 92, 1530–1534.
18. Barker, D.J.; Hales, C.N.; Fall, C.H.; Osmond, C.; Phipps, K.; Clark, P.M. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): Relation to reduced fetal growth. Diabetologia 1993, 36, 62–67.
19. Beauchamp, B.; Ghosh, S.; Dysart, M.W.; Kanaan, G.N.; Chu, A.; Blais, A.; Rajamanickam, K.; Tsai, E.C.; Patti, M.E.; Harper, M.E. Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice. Int. J. Obes. 2014, doi:10.1038/ijo.2014.120.
20. Kensara, O.A.; Wootton, S.A.; Phillips, D.I.; Patel, M.; Jackson, A.A.; Elia, M.; Hertfordshire Study, G. Fetal programming of body composition: Relation between birth weight and body composition measured with dual-energy X-ray absorptiometry and anthropometric methods in older englishmen. Am. J. Clin. Nutr. 2005, 82, 980–987.
21. Thorn, S.R.; Rozance, P.J.; Brown, L.D.; Hay, W.W., Jr. The intrauterine growth restriction phenotype: Fetal adaptations and potential implications for later life insulin resistance and diabetes. Semin. Reprod. Med. 2011, 29, 225–236.
22. Gluckman, P.D.; Hanson, M.A.; Spencer, H.G.; Bateson, P. Environmental influences during development and their later consequences for health and disease: Implications for the interpretation of empirical studies. Proc. Biol. Sci. R. Soc. 2005, 272, 671–677.
23. DeFronzo, R.A.; Jacot, E.; Jequier, E.; Maeder, E.; Wahren, J.; Felber, J.P. The effect of insulin on the disposal of intravenous glucose: Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 1981, 30, 1000–1007.
24. Zurlo, F.; Nemeth, P.M.; Choksi, R.M.; Sesodia, S.; Ravussin, E. Whole-body energy metabolism and skeletal muscle biochemical characteristics. Metab. Clin. Exp. 1994, 43, 481–486.
25. Yu, C.; Chen, Y.; Cline, G.W.; Zhang, D.; Zong, H.; Wang, Y.; Bergeron, R.; Kim, J.K.; Cushman, S.W.; Cooney, G.J.; et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J. Biol. Chem. 2002, 277, 50230–50236.
26. Koves, T.R.; Ussher, J.R.; Noland, R.C.; Slentz, D.; Mosedale, M.; Ilkayeva, O.; Bain, J.; Stevens, R.; Dyck, J.R.; Newgard, C.B.; et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 2008, 7, 45–56.
27. Shulman, G.I. Cellular mechanisms of insulin resistance. J. Clin. Investig. 2000, 106, 171–176.
28. Zierath, J.R.; Krook, A.; Wallberg-Henriksson, H. Insulin action and insulin resistance in human skeletal muscle. Diabetologia 2000, 43, 821–835.
29. Blesson, C.S.; Sathishkumar, K.; Chinnathambi, V.; Yallampalli, C. Gestational protein restriction impairs insulin regulated glucose transport mechanisms in gastrocnemius muscles of adult male offspring. Endocrinology 2014, doi:10.1210/en.2014-1094.
30. Owens, J.A.; Thavaneswaran, P.; De Blasio, M.J.; McMillen, I.C.; Robinson, J.S.; Gatford, K.L. Sex-specific effects of placental restriction on components of the metabolic syndrome in young adult sheep. Am. J. Physiol. Endocrinol. Metab. 2007, 292, E1879–E1889.
31. De Blasio, M.J.; Gatford, K.L.; Harland, M.L.; Robinson, J.S.; Owens, J.A. Placental restriction reduces insulin sensitivity and expression of insulin signaling and glucose transporter genes in skeletal muscle, but not liver, in young sheep. Endocrinology 2012, 153, 2142–2151.
32. De Blasio, M.J.; Gatford, K.L.; McMillen, I.C.; Robinson, J.S.; Owens, J.A. Placental restriction of fetal growth increases insulin action, growth, and adiposity in the young lamb. Endocrinology 2007, 148, 1350–1358.
33. Sugden, M.C.; Holness, M.J. Gender-specific programming of insulin secretion and action. J. Endocrinol. 2002, 175, 757–767.
34. Jaquet, D.; Gaboriau, A.; Czernichow, P.; Levy-Marchal, C. Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J. Clin. Endocrinol. Metab. 2000, 85, 1401–1406.
35. Hales, C.N.; Barker, D.J.; Clark, P.M.; Cox, L.J.; Fall, C.; Osmond, C.; Winter, P.D. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991, 303, 1019–1022.
36. Ozanne, S.E.; Jensen, C.B.; Tingey, K.J.; Storgaard, H.; Madsbad, S.; Vaag, A.A. Low birthweight is associated with specific changes in muscle insulin-signalling protein expression. Diabetologia 2005, 48, 547–552.
37. Thorn, S.R.; Regnault, T.R.; Brown, L.D.; Rozance, P.J.; Keng, J.; Roper, M.; Wilkening, R.B.; Hay, W.W., Jr.; Friedman, J.E. Intrauterine growth restriction increases fetal hepatic gluconeogenic capacity and reduces messenger ribonucleic acid translation initiation and nutrient sensing in fetal liver and skeletal muscle. Endocrinology 2009, 150, 3021–3030.
38. Oak, S.A.; Tran, C.; Pan, G.; Thamotharan, M.; Devaskar, S.U. Perturbed skeletal muscle insulin signaling in the adult female intrauterine growth-restricted rat. Am. J. Physiol. Endocrinol. Metab. 2006, 290, E1321–E1330.
39. Copps, K.D.; White, M.F. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins irs1 and IRS2. Diabetologia 2012, 55, 2565–2582.
40. Karlsson, H.K.; Zierath, J.R.; Kane, S.; Krook, A.; Lienhard, G.E.; Wallberg-Henriksson, H. Insulin-stimulated phosphorylation of the AKT substrate as160 is impaired in skeletal muscle of type 2 diabetic subjects. Diabetes 2005, 54, 1692–1697.
41. Holemans, K.; Verhaeghe, J.; Dequeker, J.; van Assche, F.A. Insulin sensitivity in adult female rats subjected to malnutrition during the perinatal period. J. Soc. Gynecol. Investig. 1996, 3, 71–77.
42. Stein, J.M.; Padykula, H.A. Histochemical classification of individual skeletal muscle fibers of the rat. Am. J. Anat. 1962, 110, 103–123.
43. Leary, S.C.; Lyons, C.N.; Rosenberger, A.G.; Ballantyne, J.S.; Stillman, J.; Moyes, C.D. Fiber-type differences in muscle mitochondrial profiles. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003, 285, R817–R826.
44. Peter, J.B.; Barnard, R.J.; Edgerton, V.R.; Gillespie, C.A.; Stempel, K.E. Metabolic profiles of three fiber types of skeletal muscle in guinea pigs and rabbits. Biochemistry 1972, 11, 2627–2633.
45. Selak, M.A.; Storey, B.T.; Peterside, I.; Simmons, R.A. Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth-retarded rats. Ame. J. Physiol. Endocrinol. Metab. 2003, 285, E130–E137.
46. Peterside, I.E.; Selak, M.A.; Simmons, R.A. Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats. Am. J. Physiol. Endocrinol. Metab. 2003, 285, 1258–1266.
47. Albrecht, E.; Lembcke, C.; Wegner, J.; Maak, S. Prenatal muscle fiber development and bundle structure in beef and dairy cattle. J. Anim. Sci. 2013, 91, 3666–3673.
48. St-Pierre, J.; Lin, J.; Krauss, S.; Tarr, P.T.; Yang, R.; Newgard, C.B.; Spiegelman, B.M. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J. Biol. Chem. 2003, 278, 26597–26603.
49. Limesand, S.W.; Rozance, P.J.; Smith, D.; Hay, W.W., Jr. Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction. Am. J. Physiol. Endocrinol. Metab. 2007, 293, E1716–E1725.
50. Bauer, R.; Walter, B.; Brust, P.; Füchtner, F.; Zwiener, U. Impact of asymmetric intrauterine growth restriction on organ function in newborn piglets. Eur. J. Obstetrics Gynecol. Reprod. Biol. 2003, 110, S40–S49.
51. Wank, V.; Bauer, R.; Walter, B.; Kluge, H.; Fischer, M.S.; Blickhan, R.; Zwiener, U. Accelerated contractile function and improved fatigue resistance of calf muscles in newborn piglets with IUGR. Am. J. Physiol. Regul. Integ. Comp. Physiol. 2000, 278, R304–R310.
52. Bauer, R.; Gedrange, T.; Bauer, K.; Walter, B. Intrauterine growth restriction induces increased capillary density and accelerated type I fiber maturation in newborn pig skeletal muscles. J. Perinat. Med. 2006, 34, 235–242.
53. He, J.; Watkins, S.; Kelley, D.E. Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle fiber type in type 2 diabetes and obesity. Diabetes 2001, 50, 817–823.
54. Oberbach, A.; Bossenz, Y.; Lehmann, S.; Niebauer, J.; Adams, V.; Paschke, R.; Schon, M.R.; Bluher, M.; Punkt, K. Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes. Diabetes Care 2006, 29, 895–900.
55. Reusch, J.E.; Bridenstine, M.; Regensteiner, J.G. Type 2 diabetes mellitus and exercise impairment. Rev. Endocr. Metab. Disord. 2013, 14, 77–86.
56. Badin, P.M.; Langin, D.; Moro, C. Dynamics of skeletal muscle lipid pools. Trends Endocrinol. Metab. TEM 2013, 24, 607–615.
57. Abdul-Ghani, M.A.; DeFronzo, R.A. Pathogenesis of insulin resistance in skeletal muscle. J. Biomed. Biotechnol. 2010, 2010, 476279, doi:10.1155/2010/476279.
58. Zhang, L.; Keung, W.; Samokhvalov, V.; Wang, W.; Lopaschuk, G.D. Role of fatty acid uptake and fatty acid beta-oxidation in mediating insulin resistance in heart and skeletal muscle. Biochim. Biophys. Acta 2010, 1801, 1–22.
59. Storlien, L.H.; Jenkins, A.B.; Chisholm, D.J.; Pascoe, W.S.; Khouri, S.; Kraegen, E.W. Influence of dietary fat composition on development of insulin resistance in rats: Relationship to muscle triglyceride and ω-3 fatty acids in muscle phospholipid. Diabetes 1991, 40, 280–289.
60. Kewalramani, G.; Bilan, P.J.; Klip, A. Muscle insulin resistance: Assault by lipids, cytokines and local macrophages. Curr. Opin. Clin. Nutr. Metabo. Care 2010, 13, 382–390.
61. Dziewulska, A.; Dobrzyn, P.; Jazurek, M.; Pyrkowska, A.; Ntambi, J.M.; Dobrzyn, A. Monounsaturated fatty acids are required for membrane translocation of protein kinase C-theta induced by lipid overload in skeletal muscle. Mol. Memb. Biol. 2012, 29, 309–320.
62. Lee, J.S.; Pinnamaneni, S.K.; Eo, S.J.; Cho, I.H.; Pyo, J.H.; Kim, C.K.; Sinclair, A.J.; Febbraio, M.A.; Watt, M.J. Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: Role of intramuscular accumulation of lipid metabolites. J. Appl. Physiol. 2006, 100, 1467–1474.
63. Kelley, D.E.; Goodpaster, B.; Wing, R.R.; Simoneau, J.-A. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity and weight loss. Endocrinol. MeTable 1999, 40, E1130–E1141.
64. Malenfant, P.; Joanisse, D.; Theriault, R.; Goodpaster, B.; Kelley, D.; Simoneau, J.-A. Fat content in individual muscle fibers of lean and obese subjects. Int. J. Obes. 2001, 25, 1316–1321.
65. Barucci, N.; Bell, K.; Cline, G.W.; Goodyear, L.J.; Griffin, M.E.; Kraegen, E.W.; Lee, D.; Marcucci, M.J.; Shulman, G.I.; White, M.F. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C (theta) and alterations in the insulin signaling cascade. Diabetes 1999, 48, 1270–1274.
66. Germani, D.; Puglianiello, A.; Cianfarani, S. Uteroplacental insufficiency down regulates insulin receptor and affects expression of key enzymes of long-chain fatty acid (LCFA) metabolism in skeletal muscle at birth. Cardiovasc. Diabetol. 2008, 7, 14, doi:10.1186/1475-2840-7-14.
67. Henstridge, D.C.; Bruce, C.R.; Pang, C.P.; Lancaster, G.I.; Allen, T.L.; Estevez, E.; Gardner, T.; Weir, J.M.; Meikle, P.J.; Lam, K.S.; et al. Skeletal muscle-specific overproduction of constitutively activated c-Jun N-terminal kinase (JNK) induces insulin resistance in mice. Diabetologia 2012, 55, 2769–2778.
68. Koves, T.R.; Li, P.; An, J.; Akimoto, T.; Slentz, D.; Ilkayeva, O.; Dohm, G.L.; Yan, Z.; Newgard, C.B.; Muoio, D.M. Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J. Biol. Chem. 2005, 280, 33588–33598.
69. Rutkowsky, J.M.; Knotts, T.A.; Ono-Moore, K.D.; McCoin, C.S.; Huang, S.; Schneider, D.; Singh, S.; Adams, S.H.; Hwang, D.H. Acylcarnitines activate proinflammatory signaling pathways. Am. J. Physiol. Endocrinol. Metab. 2014, 306, E1378–E1387.
70. Muoio, D.M.; Koves, T.R. Skeletal muscle adaptation to fatty acid depends on coordinated actions of the ppars and PGC1 alpha: Implications for metabolic disease. Appl. Physiol. Nutr. Metab. 2007, 32, 874–883.
71. Jacobsen, S.C.; Gillberg, L.; Bork-Jensen, J.; Ribel-Madsen, R.; Lara, E.; Calvanese, V.; Ling, C.; Fernandez, A.F.; Fraga, M.F.; Poulsen, P.; et al. Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding. Diabetologia 2014, 57, 1154–1158.
72. Sugden, M.C.; Caton, P.W.; Holness, M.J. PPAR control: It’s sirtainly as easy as PGC. J. Endocrinol. 2010, 204, 93–104.
73. Finck, B.N.; Bernal-Mizrachi, C.; Han, D.H.; Coleman, T.; Sambandam, N.; LaRiviere, L.L.; Holloszy, J.O.; Semenkovich, C.F.; Kelly, D.P. A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes. Cell Metab. 2005, 1, 133–144.
74. Liu, J.; Chen, D.; Yao, Y.; Yu, B.; Mao, X.; He, J.; Huang, Z.; Zheng, P. Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle. PLoS One 2012, 7, e34835, doi:10.1371/journal.pone.0034835.
75. Lane, R.H.; Maclennan, N.K.; Daood, M.J.; Hsu, J.L.; Janke, S.M.; Pham, T.D.; Puri, A.R.; Watchko, J.F. Iugr alters postnatal rat skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1 gene expression in a fiber specific manner. Pediatr. Res. 2003, 53, 994–1000.
76. Zeng, Y.; Gu, P.; Liu, K.; Huang, P. Maternal protein restriction in rats leads to reduced PGC-1alpha expression via altered DNA methylation in skeletal muscle. Mol. Med. Rep. 2013, 7, 306–312.
77. Brons, C.; Jacobsen, S.; Nilsson, E.; Ronn, T.; Jensen, C.B.; Storgaard, H.; Poulsen, P.; Groop, L.; Ling, C.; Astrup, A.; et al. Deoxyribonucleic acid methylation and gene expression of PPARGC1A in human muscle is influenced by high-fat overfeeding in a birth-weight-dependent manner. J. Clin. Endocrinol. Metab. 2010, 95, 3048–3056.
78. Laker, R.C.; Wlodek, M.E.; Wadley, G.D.; Gallo, L.A.; Meikle, P.J.; McConell, G.K. Exercise early in life in rats born small does not normalize reductions in skeletal muscle PGC-1alpha in adulthood. Am. J. Physiol. Endocrinol. Metab. 2012, 302, E1221–E1230.