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Mechanism of Storage and Synthesis of Fatty Acids and Triglycerides in White Adipocytes

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Abstract

Mechanism of storage and synthesis of fatty acids and triglycerides in white adipocytes Lipid storage in adipocytes is essential for energy homeostasis and has probably played a major role in the survival of our species in periods of food shortage. In adipose tissue, fatty acids are stored as triglycerides formed from a backbone of glycerol which are esterified three fatty acids. In a lean young adult human, the mass of triglycerides stored represents about 10–20 kilograms i.e. 90 000–180 000 kcal. The origin of the fatty acids stored as triglycerides is for a major part the diet. Triglycerides after their intestinal hydrolysis and resynthesis in the enterocytes are delivered as chylomicrons into the circulation. Fatty acids in adipocytes can also originate from the de novo synthesis of fatty acids from glucose in the liver (lipogenesis) delivered as “Very Low density Lipoproteins” (VLDL) into the circulation, or from lipogenesis in the adipocyte itself. Whatever their origin, exogenous or endogenous, free fatty acids are activated into acyl-CoA and esterified to finally reach the triglyceride droplet. In this review, we address the process of fatty acids delivery to the adipocytes from lipoproteins (chylomicrons and VLDL) and the specific role of lipoprotein lipase, the uptake of fatty acids by the adipocyte and their activation, their de novo synthesis and finally their esterification into triglycerides.

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References

  • Aarsland A, Chinkes D, Wolfe RR (1997) Hepatic and whole-body fat synthesis in humans during carbohydrate overfeeding. Am J Clin Nutr 65:1774–1782

    PubMed  CAS  Google Scholar 

  • 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 48:240–247

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 56:960–964

    Article  PubMed  CAS  Google Scholar 

  • 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 32:1449–1456

    PubMed  CAS  Google Scholar 

  • 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 273:110–118

    Article  PubMed  CAS  Google Scholar 

  • Ballard FJ, Hanson RW, Leveille GA (1967) Phosphoenolpyruvate carboxykinase and the synthesis of glyceride-glycerol from pyruvate in adipose tissue. J Biol Chem 242:2746–2750

    PubMed  CAS  Google Scholar 

  • 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 284:6101–6108

    Article  PubMed  CAS  Google Scholar 

  • 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 325:827–834

    Article  PubMed  CAS  Google Scholar 

  • Braun JE, Severson DL (1992) Regulation of the synthesis, processing and translocation of lipoprotein lipase. Biochem J 287(Pt 2):337–347

    PubMed  CAS  Google Scholar 

  • 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 275:32523–32529

    Article  PubMed  CAS  Google Scholar 

  • Connelly PW, Maguire GF, Hofmann T, Little JA (1987) Structure of apolipoprotein C-IIToronto, a nonfunctional human apolipoprotein. Proc Natl Acad Sci U S A 84:270–273

    Article  PubMed  CAS  Google Scholar 

  • 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 9:165–176

    Article  PubMed  CAS  Google Scholar 

  • 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 48:2788–2791

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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–E51

    PubMed  CAS  Google Scholar 

  • 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 44:846–853

    Article  PubMed  CAS  Google Scholar 

  • Dunlop M, Court JM (1978) Lipogenesis in developing human adipose tissue. Early Hum Dev 2:123–130

    Article  PubMed  CAS  Google Scholar 

  • Ellis JM, Frahm JL, Li LO, Coleman RA (2010) Acyl-coenzyme A synthetases in metabolic control. Curr Opin Lipidol 21:212–217

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 366:377–391

    Article  PubMed  CAS  Google Scholar 

  • 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 267:20543–20546

    PubMed  CAS  Google Scholar 

  • 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 51:624–630

    Article  PubMed  CAS  Google Scholar 

  • 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 876:288–293

    Article  PubMed  CAS  Google Scholar 

  • 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 

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

    PubMed  CAS  Google Scholar 

  • Gimeno RE (2007) Fatty acid transport proteins. Curr Opin Lipidol 18:271–276

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • Hallakou S, Doare L, Foufelle F et al (1997) Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes 46:1393–1399

    Article  PubMed  CAS  Google Scholar 

  • Hauner H, Skurk T, Wabitsch M (2001) Cultures of human adipose precursor cells. Methods Mol Biol 155:239–247

    PubMed  CAS  Google Scholar 

  • He Z, Jiang T, Wang Z et al (2004) Modulation of carbohydrate response element-binding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue. Am J Physiol Endocrinol Metab 287:E424–E430

    Article  PubMed  CAS  Google Scholar 

  • 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 278:36652–36660

    Article  PubMed  CAS  Google Scholar 

  • 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 U S A 83:3786–3790

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Iizuka K, Bruick RK, Liang G et al (2004) Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci U S A 101:7281–7286

    Article  PubMed  CAS  Google Scholar 

  • 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–E364

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

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

    Article  PubMed  CAS  Google Scholar 

  • Kim JB, Spiegelman BM (1996) ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev 10:1096–1107

    Article  PubMed  CAS  Google Scholar 

  • Kim JB, Wright HM, Wright M, Spiegelman BM (1998a) ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci U S A 95:4333–4337

    Article  PubMed  CAS  Google Scholar 

  • Kim JB, Sarraf P, Wright M et al (1998b) 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 

  • 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 283:34896–34906

    Article  PubMed  CAS  Google Scholar 

  • Le Lay S, Lefrere I, Trautwein C et al (2002) Insulin and sterol-regulatory element-binding 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 277:35625–35634

    Article  PubMed  Google Scholar 

  • 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 44:2127–2134

    Article  PubMed  CAS  Google Scholar 

  • Lobo S, Wiczer BM, Bernlohr DA (2009) Functional analysis of long-chain acyl-CoA synthetase 1 in 3T3-L1 adipocytes. J Biol Chem 284:18347–18356

    Article  PubMed  CAS  Google Scholar 

  • Magre J, Delepine M, Van Maldergem L et al (2003) Prevalence of mutations in AGPAT2 among human lipodystrophies. Diabetes 52:1573–1578

    Article  PubMed  CAS  Google Scholar 

  • Minehira K, Bettschart V, Vidal H et al (2003) Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans. Obes Res 11:1096–1103

    Article  PubMed  Google Scholar 

  • 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 28:1291–1298

    Article  PubMed  CAS  Google Scholar 

  • Moustaid N, Beyer RS, Sul HS (1994) Identification of an insulin response element in the fatty acid synthase promoter. J Biol Chem 269:5629–5634

    PubMed  CAS  Google Scholar 

  • Nye C, Kim J, Kalhan SC, Hanson RW (2008) Reassessing triglyceride synthesis in adipose tissue. Trends Endocrinol Metab 19:356–361

    Article  PubMed  CAS  Google Scholar 

  • Patel MS, Owen OE, Goldman LI, Hanson RW (1975) Fatty acid synthesis by human adipose tissue. Metabolism 24:161–173

    Article  PubMed  CAS  Google Scholar 

  • 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 27:121–124

    Article  PubMed  CAS  Google Scholar 

  • Peterfy M, Ben-Zeev O, Mao HZ et al (2007) Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia. Nat Genet 39:1483–1487

    Article  PubMed  CAS  Google Scholar 

  • Peters SJ (2003) Regulation of PDH activity and isoform expression: diet and exercise. Biochem Soc Trans 31:1274–1280

    Article  PubMed  CAS  Google Scholar 

  • Peterson TR, Sengupta SS, Harris TE et al (2011) mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell 146:408–420

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Postic C, Dentin R, Denechaud PD, Girard J (2007) ChREBP, a transcriptional regulator of glucose and lipid metabolism. Annu Rev Nutr 27:179–192

    Article  PubMed  CAS  Google Scholar 

  • 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 13:471–481

    Article  PubMed  CAS  Google Scholar 

  • 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 52:882–890

    Article  PubMed  CAS  Google Scholar 

  • Saleh J, Al-Wardy N, Farhan H et al (2011) Acylation stimulating protein: a female lipogenic factor? Obes Rev 12:440–448

    Article  PubMed  CAS  Google Scholar 

  • 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 15:5336–5348

    PubMed  CAS  Google Scholar 

  • 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 304:323–334

    Article  PubMed  CAS  Google Scholar 

  • Sekiya M, Yahagi N, Matsuzaka T et al (2007) SREBP-1-independent regulation of lipogenic gene expression in adipocytes. J Lipid Res 48:1581–1591

    Article  PubMed  CAS  Google Scholar 

  • 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 100:2115–2124

    Article  PubMed  CAS  Google Scholar 

  • 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 99:838–845

    Article  PubMed  CAS  Google Scholar 

  • 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 12:3182–3194

    Article  PubMed  CAS  Google Scholar 

  • Shrago E, Spennetta T, Gordon E (1969) Fatty acid synthesis in human adipose tissue. J Biol Chem 244:2761–2766

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • 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 88:5433–5437

    Article  PubMed  CAS  Google Scholar 

  • Soupene E, Kuypers FA (2008) Mammalian long-chain acyl-CoA synthetases. Exp Biol Med (Maywood) 233:507–521

    Article  CAS  Google Scholar 

  • Storch J, McDermott L (2009) Structural and functional analysis of fatty acid-binding proteins. J Lipid Res 50(Suppl):S126–S131

    Article  PubMed  Google Scholar 

  • 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 U S A 103:17450–17455

    Article  PubMed  CAS  Google Scholar 

  • 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–E1209

    Article  PubMed  CAS  Google Scholar 

  • 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 13:4753–4759

    PubMed  CAS  Google Scholar 

  • Tontonoz P, Hu E, Spiegelman BM (1995a) Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor gamma. Curr Opin Genet Dev 5:571–576

    Article  PubMed  CAS  Google Scholar 

  • Tontonoz P, Hu E, Devine J et al (1995b) PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol 15:351–357

    PubMed  CAS  Google Scholar 

  • 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–C1170

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Eckel RH (2009) Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab 297:E271–E288

    Article  PubMed  CAS  Google Scholar 

  • Wendel AA, Lewin TM, Coleman RA (2009) Glycerol-3-phosphate acyltransferases: rate limiting enzymes of triacylglycerol biosynthesis. Biochim Biophys Acta 1791:501–506

    Article  PubMed  CAS  Google Scholar 

  • 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 82:219–225

    Article  PubMed  CAS  Google Scholar 

  • 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 26:3455–3467

    Article  PubMed  CAS  Google Scholar 

  • 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 U S A 98:9116–9121

    Article  PubMed  CAS  Google Scholar 

  • Yasruel Z, Cianflone K, Sniderman AD et al (1991) Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. Lipids 26:495–499

    Article  PubMed  CAS  Google Scholar 

  • Yen CL, Stone SJ, Koliwad S et al (2008) Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res 49:2283–2301

    Article  PubMed  CAS  Google Scholar 

  • Yu YH, Ginsberg HN (2004) The role of acyl-CoA:diacylglycerol acyltransferase (DGAT) in energy metabolism. Ann Med 36:252–261

    Article  PubMed  CAS  Google Scholar 

  • Zeharia A, Shaag A, Houtkooper RH et al (2008) Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood. Am J Hum Genet 83:489–494

    Article  PubMed  CAS  Google Scholar 

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Foufelle, F., Ferré, P. (2013). Mechanism of Storage and Synthesis of Fatty Acids and Triglycerides in White Adipocytes. In: Bastard, JP., Fève, B. (eds) Physiology and Physiopathology of Adipose Tissue. Springer, Paris. https://doi.org/10.1007/978-2-8178-0343-2_8

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