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Mécanisme de stockage et de synthèse des acides gras et des triglycérides dans le tissu adipeux blanc

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Physiologie et physiopathologie du tissu adipeux
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Résumé

Dans le tissu adipeux (TA) blanc, les acides gras sont stockés sous forme de triglycérides formés d’une molécule de glycérol sur laquelle sont estérifiés trois acides gras. Chez un jeune adulte sans surpoids, le poids de triglycérides stockés représente environ 10–20 kg soit 90 000 à 180 000 kcal. Cette énergie peut être libérée sous la forme d’acides gras en cas de carence énergétique pour les besoins des organes oxydatifs comme les muscles squelettiques (fibres rouges), le cœur, le cortex rénal, le foie. Le cerveau ne peut utiliser les acides gras (ils ne passent pas la barrière hémato-encéphalique), mais peut oxyder leurs métabolites produits par le foie, les corps cétoniques. Le stockage des triglycérides dans le TA permet de survivre à 60–70 jours de jeûne chez l’homme comme on a pu le constater dans des situations extrêmes. En cas d’obésité, la période de survie peut être étendue à 90–100 jours (3 mois!). Cette capacité à jeûner pendant de longues périodes était probablement une condition nécessaire à la survie de notre espèce. Elle est malheureusement toujours essentielle dans les pays confrontés à des périodes de famine.

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Références

  1. Hussain MM (2000) A proposed model for the assembly of chylomicrons. Atherosclerosis 148: 1–15

    Article  PubMed  CAS  Google Scholar 

  2. Braun JE, Severson DL (1992) Regulation of the synthesis, processing and translocation of lipoprotein lipase. Biochem J 287 (Pt 2): 337–47.

    PubMed  CAS  Google Scholar 

  3. Dallinga-Thie GM, Zonneveld-de Boer AJ, van Vark-van der Zee LC et al. (2007) Appraisal of hepatic lipase and lipoprotein lipase activities in mice. J Lipid Res 48: 2788–91

    Article  PubMed  CAS  Google Scholar 

  4. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM et al. (1996) PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 15: 5336–48

    PubMed  CAS  Google Scholar 

  5. Schoonjans K, Gelman L, Haby C et al. (2000) Induction of LPL gene expression by sterols is mediated by a sterol regulatory element and is independent of the presence of multiple E boxes. J Mol Biol 304: 323–34

    Article  PubMed  CAS  Google Scholar 

  6. Peterfy M, Ben-Zeev O, Mao HZ et al. (2007) Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia. Nat Genet 39: 1483–7

    Article  PubMed  CAS  Google Scholar 

  7. Connelly PW, Maguire GF, Hofmann T, Little JA (1987) Structure of apolipoprotein C-IIToronto, a nonfunctional human apolipoprotein. Proc Natl Acad Sci États-Unis 84: 270–3

    Article  CAS  Google Scholar 

  8. Sukonina V, Lookene A, Olivecrona T, Olivecrona G (2006) Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue. Proc Natl Acad Sci États-Unis 103: 17450–5

    Article  CAS  Google Scholar 

  9. Fielding BA, Frayn KN (1998) Lipoprotein lipase and the disposition of dietary fatty acids. Br J Nutr 80: 495–502

    PubMed  CAS  Google Scholar 

  10. Wang H, Eckel RH (2009) Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab 297: E271–88

    Article  PubMed  CAS  Google Scholar 

  11. Preiss-Landl K, Zimmermann R, Hammerle G, Zechner R (2002) Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism. Curr Opin Lipidol 13: 471–81

    Article  PubMed  CAS  Google Scholar 

  12. Kazantzis M, Stahl A (2011) Fatty acid transport proteins, implications in physiology and disease. Biochim Biophys Acta Sep 25. [Epub ahead of print]

    Google Scholar 

  13. Gimeno RE (2007) Fatty acid transport proteins. Curr Opin Lipidol 18: 271–6

    Article  PubMed  CAS  Google Scholar 

  14. Wu Q, Ortegon AM, Tsang B et al. (2006) FATP1 is an insulin-sensitive fatty acid transporter involved in diet-induced obesity. Mol Cell Biol 26: 3455–67

    Article  PubMed  CAS  Google Scholar 

  15. Hajri T, Abumrad NA (2002) Fatty acid transport across membranes: relevance to nutrition and metabolic pathology. Annu Rev Nutr 22: 383–415

    Article  PubMed  CAS  Google Scholar 

  16. Silverstein RL, Febbraio M (2009) CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal 2: re3

    Article  PubMed  Google Scholar 

  17. Coburn CT, Knapp FF Jr, Febbraio M et al. (2000) Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J Biol Chem 275: 32523–9

    Article  PubMed  CAS  Google Scholar 

  18. Furuhashi M, Hotamisligil GS (2008) Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 7: 489–503

    Article  PubMed  CAS  Google Scholar 

  19. Storch J, McDermott L (2009) Structural and functional analysis of fatty acid-binding proteins. J Lipid Res 50 Suppl: S126–31

    Article  Google Scholar 

  20. Hunt CR, Ro JH, Dobson DE et al. (1986) Adipocyte P2 gene: developmental expression and homology of 5’-flanking sequences among fat cell-specific genes. Proc Natl Acad Sci États-Unis 83: 3786–90

    Article  CAS  Google Scholar 

  21. Amri EZ, Bertrand B, Ailhaud G, Grimaldi P (1991) Regulation of adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. J Lipid Res 32: 1449–56

    PubMed  CAS  Google Scholar 

  22. Ballard FJ (1972) Effects of fasting and refeeding on the concentrations of glycolytic intermediates and the regulation of lipogenesis in rat adipose tissue in vivo. Biochim Biophys Acta 273: 110–8

    Article  PubMed  CAS  Google Scholar 

  23. Peters SJ (2003) Regulation of PDH activity and isoform expression: diet and exercise. Biochem Soc Trans 31: 1274–80

    Article  PubMed  CAS  Google Scholar 

  24. Wan Z, Thrush AB, Legare M et al. (2010) Epinephrine-mediated regulation of PDK4 mRNA in rat adipose tissue. Am J Physiol Cell Physiol 299: C1162–70

    Article  PubMed  CAS  Google Scholar 

  25. Denton RM, Brownsey RW (1983) The role of phosphorylation in the regulation of fatty acid synthesis by insulin and other hormones. Philos Trans R Soc Lond B Biol Sci 302: 33–45

    Article  PubMed  CAS  Google Scholar 

  26. Kim KH (1997) Regulation of mammalian acetyl-coenzyme A carboxylase. Annu Rev Nutr 17: 77–99

    Article  PubMed  CAS  Google Scholar 

  27. Winder WW, Wilson HA, Hardie DG et al. (1997) Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. J Appl Physiol 82: 219–25

    Article  PubMed  CAS  Google Scholar 

  28. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1: 15–25

    Article  PubMed  CAS  Google Scholar 

  29. Foufelle F, Ferre P (2002) New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J 366: 377–91

    Article  PubMed  CAS  Google Scholar 

  30. Foufelle F, Gouhot B, Pegorier JP et al. (1992) Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate. J Biol Chem 267: 20543–6

    PubMed  CAS  Google Scholar 

  31. Moustaid N, Beyer RS, Sul HS (1994) Identification of an insulin response element in the fatty acid synthase promoter. J Biol Chem 269: 5629–34

    PubMed  CAS  Google Scholar 

  32. Postic C, Dentin R, Denechaud PD, Girard J (2007) ChREBP, a transcriptional regulator of glucose and lipid metabolism. Annu Rev Nutr 27: 179–92

    Article  PubMed  CAS  Google Scholar 

  33. Shimomura I, Shimano H, Horton JD et al. (1997) Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest 99: 838–45

    Article  PubMed  CAS  Google Scholar 

  34. Tontonoz P, Kim JB, Graves RA, Spiegelman BM (1993) ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Mol Cell Biol 13: 4753–9

    PubMed  CAS  Google Scholar 

  35. Kim JB, Spiegelman BM (1996) ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev 10: 1096–107

    Article  PubMed  CAS  Google Scholar 

  36. Kim JB, Wright HM, Wright M, Spiegelman BM (1998) ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci États-Unis 95: 4333–7

    Article  CAS  Google Scholar 

  37. Kim JB, Sarraf P, Wright M et al. (1998) Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 101: 1–9

    Article  PubMed  CAS  Google Scholar 

  38. Le Lay S, Lefrere I, Trautwein C et al. (2002) Insulin and sterol-regulatory elementbinding protein-1c (SREBP-1C) regulation of gene expression in 3T3-L1 adipocytes. Identification of CCAAT/enhancer-binding protein beta as an SREBP-1C target. J Biol Chem 277: 35625–34

    Article  PubMed  Google Scholar 

  39. Letexier D, Pinteur C, Large V et al. (2003) Comparison of the expression and activity of the lipogenic pathway in human and rat adipose tissue. J Lipid Res 44: 2127–34

    Article  PubMed  CAS  Google Scholar 

  40. Bertile F, Raclot T (2004) mRNA levels of SREBP-1c do not coincide with the changes in adipose lipogenic gene expression. Biochem Biophys Res Commun 325: 827–34

    Article  PubMed  CAS  Google Scholar 

  41. Shimano H, Shimomura I, Hammer RE et al. (1997) Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J Clin Invest 100: 2115–24

    Article  PubMed  CAS  Google Scholar 

  42. Sekiya M, Yahagi N, Matsuzaka T et al. (2007) SREBP-1-independent regulation of lipogenic gene expression in adipocytes. J Lipid Res 48: 1581–91

    Article  PubMed  CAS  Google Scholar 

  43. Shimomura I, Hammer RE, Richardson JA et al. (1998) Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev 12: 3182–94

    Article  PubMed  CAS  Google Scholar 

  44. Horton JD, Shimomura I, Ikemoto S et al. (2003) Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver. J Biol Chem 278: 36652–60

    Article  PubMed  CAS  Google Scholar 

  45. Yamashita H, Takenoshita M, Sakurai M et al. (2001) A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proc Natl Acad Sci États-Unis 98: 9116–21

    Article  CAS  Google Scholar 

  46. He Z, Jiang T, Wang Z et al. (2004) Modulation of carbohydrate response elementbinding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue. Am J Physiol Endocrinol Metab 287: E424–30

    Article  PubMed  CAS  Google Scholar 

  47. Iizuka K, Bruick RK, Liang G et al. (2004) Deficiency of carbohydrate response elementbinding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci États-Unis 101: 7281–6

    Article  CAS  Google Scholar 

  48. Iizuka K, Miller B, Uyeda K (2006) Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob/ob) mice. Am J Physiol Endocrinol Metab 291: E358–64

    Article  PubMed  CAS  Google Scholar 

  49. Shrago E, Spennetta T, Gordon E (1969) Fatty acid synthesis in human adipose tissue. J Biol Chem 244: 2761–6

    PubMed  CAS  Google Scholar 

  50. Patel MS, Owen OE, Goldman LI, Hanson RW (1975) Fatty acid synthesis by human adipose tissue. Metabolism 24: 161–73

    Article  PubMed  CAS  Google Scholar 

  51. Galton DJ (1968) Lipogenesis in human adipose tissue. J Lipid Res 9: 19–26

    PubMed  CAS  Google Scholar 

  52. Diraison F, Yankah V, Letexier D et al. (2003) Differences in the regulation of adipose tissue and liver lipogenesis by carbohydrates in humans. J Lipid Res 44: 846–53

    Article  PubMed  CAS  Google Scholar 

  53. Acheson KJ, Schutz Y, Bessard T et al. (1988) Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am J Clin Nutr 48: 240–7

    PubMed  CAS  Google Scholar 

  54. Aarsland A, Chinkes D, Wolfe RR (1997) Hepatic and whole-body fat synthesis in humans during carbohydrate overfeeding. Am J Clin Nutr 65: 1774–82

    PubMed  CAS  Google Scholar 

  55. Minehira K, Bettschart V, Vidal H et al. (2003) Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans. Obes Res 11: 1096–103

    Article  PubMed  Google Scholar 

  56. Diraison F, Dusserre E, Vidal H et al. (2002) Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity. Am J Physiol Endocrinol Metab 282: E46–51

    PubMed  CAS  Google Scholar 

  57. Hauner H, Skurk T, Wabitsch M (2001) Cultures of human adipose precursor cells. Methods Mol Biol 155: 239–47

    PubMed  CAS  Google Scholar 

  58. Minehira K, Vega N, Vidal H et al. (2004) Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans. Int J Obes Relat Metab Disord 28: 1291–8

    Article  PubMed  CAS  Google Scholar 

  59. Roberts R, Hodson L, Dennis AL et al. (2009) Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans. Diabetologia 52: 882–90

    Article  PubMed  CAS  Google Scholar 

  60. Dunlop M, Court JM (1978) Lipogenesis in developing human adipose tissue. Early Hum Dev 2: 123–30

    Article  PubMed  CAS  Google Scholar 

  61. Ellis JM, Frahm JL, Li LO, Coleman RA (2010) Acyl-coenzyme A synthetases in metabolic control. Curr Opin Lipidol 21: 212–7

    Article  PubMed  CAS  Google Scholar 

  62. Soupene E, Kuypers FA (2008) Mammalian long-chain acyl-CoA synthetases. Exp Biol Med (Maywood) 233: 507–21

    Article  CAS  Google Scholar 

  63. Tontonoz P, Hu E, Spiegelman BM (1995) Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor gamma. Curr Opin Genet Dev 5: 571–6

    Article  PubMed  CAS  Google Scholar 

  64. Lobo S, Wiczer BM, Bernlohr DA (2009) Functional analysis of long-chain acyl-CoA synthetase 1 in 3T3-L1 adipocytes. J Biol Chem 284: 18347–56

    Article  PubMed  CAS  Google Scholar 

  65. Fredrikson G, Tornqvist H, Belfrage P (1986) Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. Biochim Biophys Acta 876: 288–93

    Article  PubMed  CAS  Google Scholar 

  66. Takeuchi K, Reue K (2009) Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am J Physiol Endocrinol Metab 296: E1195–209

    Article  PubMed  CAS  Google Scholar 

  67. Wendel AA, Lewin TM, Coleman RA (2009) Glycerol-3-phosphate acyltransferases: rate limiting enzymes of triacylglycerol biosynthesis. Biochim Biophys Acta 1791: 501–6

    Article  PubMed  CAS  Google Scholar 

  68. Agarwal AK, Arioglu E, De Almeida S et al. (2002) AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nat Genet 31: 21–23

    Article  PubMed  CAS  Google Scholar 

  69. Magre J, Delepine M, Van Maldergem L et al. (2003) Prevalence of mutations in AGPAT2 among human lipodystrophies. Diabetes 52: 1573–8

    Article  PubMed  CAS  Google Scholar 

  70. Simha V, Garg A (2003) Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes. J Clin Endocrinol Metab 88: 5433–7

    Article  PubMed  CAS  Google Scholar 

  71. Cortes VA, Curtis DE, Sukumaran S et al. (2009) Molecular mechanisms of hepatic steatosis and insulin resistance in the AGPAT2-deficient mouse model of congenital generalized lipodystrophy. Cell Metab 9: 165–76

    Article  PubMed  CAS  Google Scholar 

  72. Peterfy M, Phan J, Xu P, Reue K (2001) Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat Genet 27: 121–4

    Article  PubMed  CAS  Google Scholar 

  73. Phan J, Reue K (2005) Lipin, a lipodystrophy and obesity gene. Cell Metab 1: 73–83

    Article  PubMed  CAS  Google Scholar 

  74. Zeharia A, Shaag A, Houtkooper RH et al. (2008) Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood. Am J Hum Genet 83: 489–94

    Article  PubMed  CAS  Google Scholar 

  75. Al-Mosawi ZS, Al-Saad KK, Ijadi-Maghsoodi R et al. (2007) A splice site mutation confirms the role of LPIN2 in Majeed syndrome. Arthritis Rheum 56: 960–4

    Article  PubMed  CAS  Google Scholar 

  76. Gomez-Munoz A, Hamza EH, Brindley DN (1992) Effects of sphingosine, albumin and unsaturated fatty acids on the activation and translocation of phosphatidate phosphohydrolases in rat hepatocytes. Biochim Biophys Acta 1127: 49–56

    Article  PubMed  CAS  Google Scholar 

  77. Finck BN, Gropler MC, Chen Z et al. (2006) Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway. Cell Metab 4: 199–210

    Article  PubMed  CAS  Google Scholar 

  78. Koh YK, Lee MY, Kim JW et al. (2008) Lipin1 is a key factor for the maturation and maintenance of adipocytes in the regulatory network with CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma 2. J Biol Chem 283: 34896–906

    Article  PubMed  CAS  Google Scholar 

  79. Peterson TR, Sengupta SS, Harris TE et al. (2011) mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell 146: 408–20

    Article  PubMed  CAS  Google Scholar 

  80. Yu YH, Ginsberg HN (2004) The role of acyl-CoA:diacylglycerol acyltransferase (DGAT) in energy metabolism. Ann Med 36: 252–61

    Article  PubMed  CAS  Google Scholar 

  81. Yen CL, Stone SJ, Koliwad S et al. (2008) Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res 49: 2283–301

    Article  PubMed  CAS  Google Scholar 

  82. Yasruel Z, Cianflone K, Sniderman AD et al. (1991) Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. Lipids 26: 495–9

    Article  PubMed  CAS  Google Scholar 

  83. Saleh J, Al-Wardy N, Farhan H et al. (2011) Acylation stimulating protein: a female lipogenic factor? Obes Rev 12: 440–8

    Article  PubMed  CAS  Google Scholar 

  84. FJ, Hanson RW, Leveille GA (1967) Phosphoenolpyruvate carboxykinase and the synthesis of glyceride-glycerol from pyruvate in adipose tissue. J Biol Chem 242: 2746–50

    Google Scholar 

  85. Nye C, Kim J, Kalhan SC, Hanson RW (2008) Reassessing triglyceride synthesis in adipose tissue. Trends Endocrinol Metab 19: 356–61

    Article  PubMed  CAS  Google Scholar 

  86. Bederman IR, Foy S, Chandramouli V et al. (2009) Triglyceride synthesis in epididymal adipose tissue: contribution of glucose and non-glucose carbon sources. J Biol Chem 284: 6101–8

    Article  PubMed  CAS  Google Scholar 

  87. Tontonoz P, Hu E, Devine J et al. (1995) PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol 15: 351–7

    PubMed  CAS  Google Scholar 

  88. Hallakou S, Doare L, Foufelle F et al. (1997) Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes 46: 1393–9

    Article  PubMed  CAS  Google Scholar 

  89. Franckhauser S, Munoz S, Pujol A et al. (2002) Increased fatty acid re-esterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance. Diabetes 51: 624–30

    Article  PubMed  CAS  Google Scholar 

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Foufelle, F., Ferré, P. (2013). Mécanisme de stockage et de synthèse des acides gras et des triglycérides dans le tissu adipeux blanc. In: Physiologie et physiopathologie du tissu adipeux. Springer, Paris. https://doi.org/10.1007/978-2-8178-0332-6_8

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