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Vitamin A and lipid metabolism: relationship between hepatic stellate cells (HSCs) and adipocytes

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Abstract

Vitamin A or retinol plays a major role in the regulation of cellular homeostasis. Retinyl palmitate remains the main chemical form of vitamin A storage and is mainly located in hepatic stellate cells (HSCs) in lipid droplets resembling those found in adipose cells. White adipose tissue (WAT), is essentially involved in the regulation of lipid metabolism, through its role in lipid storage, and might also be considered as a vitamin A storage and metabolism site. WAT contains all the intracellular equipment for vitamin A metabolism and signaling pathways which allows retinol to be metabolized into retinoic acid, known to control genomic expression in WAT. The description of molecular mechanisms involved in the activation of HSCs and the differentiation of preadipocytes reveal similar cellular and molecular mechanisms. Indeed HSCs and adipocytes share a common expression of key transcription factors like PPAR-γ and RXR known to influence perilipin expression, which play fundamental roles in lipid droplet metabolism. Both cells are also sources of important endocrine signaling secretions influencing the expression of these transcription factors. The morphological and functional characteristics of HSCs and adipocytes, including the metabolism of vitamin A and other lipids and their related signaling pathways, are summarized and compared in this review. We highlight the complexity of the interrelationship between lipids and vitamin A metabolism and the role of the complex communication existing between HSCs and WAT in diseases such as non-alcoholic fatty liver disease which is the hepatic manifestation of the metabolic syndrome.

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References

  1. Abergel A, Sapin V, Dif N, Chassard C, Darcha C, Marcand-Sauvant J, Gaillard-Martinie B, Rock E, Dechelotte P, Sauvant P (2006) Growth arrest and decrease of alpha-SMA and type I collagen expression by palmitic acid in the rat hepatic stellate cell line PAV-1. Dig Dis Sci 51:986–995

    Article  PubMed  CAS  Google Scholar 

  2. Armani A, Mammi C, Marzolla V, Calanchini M, Antelmi A, Rosano GM, Fabbri A, Caprio M (2010) Cellular models for understanding adipogenesis, adipose dysfunction, and obesity. J Cell Biochem 110:564–572

    Article  PubMed  CAS  Google Scholar 

  3. Arthur MJ (2000) Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 279:G245–G249

    PubMed  CAS  Google Scholar 

  4. Bairras C, Menard L, Redonnet A, Ferrand C, Delage B, Noel-Suberville C, Atgié C, Higueret P (2005) Effect of vitamin A content in cafeteria diet on the expression of nuclear receptors in rat subcutaneous adipose tissue. J Physiol Biochem 61:353–361

    Article  PubMed  CAS  Google Scholar 

  5. Beaven SW, Wroblewski K, Wang J, Hong C, Bensinger S, Tsukamoto H, Tontonoz P (2011) Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease. Gastroenterology 140:1052–1062

    Article  PubMed  CAS  Google Scholar 

  6. Bickel PE, Tansey JT, Welte MA (2009) PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochim Biophys Acta 1791:419–440

    PubMed  CAS  Google Scholar 

  7. Blaner WS, O'Byrne SM, Wongsiriroj N, Kluwe J, D'Ambrosio DM, Jiang H, Schwabe RF, Hillman EM, Piantedosi R, Libien J (2009) Hepatic stellate cell lipid droplets: a specialized lipid droplet for retinoid storage. Biochim Biophys Acta 1791:467–473

    PubMed  CAS  Google Scholar 

  8. Blomhoff R, Green MH, Berg T, Norum KR (1990) Transport and storage of vitamin A. Science 250:399–404

    Article  PubMed  CAS  Google Scholar 

  9. Blomhoff R, Blomhoff HK (2006) Overview of retinoid metabolism and function. J Neurobiol 66:606–630

    Article  PubMed  CAS  Google Scholar 

  10. Bonet ML, Ribot J, Felipe F, Palou A (2003) Vitamin A and the regulation of fat reserves. Cell Mol Life Sci 60:1311–1321

    Article  PubMed  CAS  Google Scholar 

  11. Borojevic R, Monteiro AN, Vinhas SA, Domont GB, Mourao PA, Emonard H, Grimaldi G Jr, Grimaud JA (1985) Establishment of a continuous cell line from fibrotic schistosomal granulomas in mice livers. In Vitro Cell Dev Biol 21:382–390

    Article  PubMed  CAS  Google Scholar 

  12. Caspar-Bauguil S, Cousin B, Bour S, Castiella L, Penicaud L, Carpene C (2009) Adipose tissue lymphocytes: types and roles. J Physiol Biochem 65:423–436

    Article  PubMed  CAS  Google Scholar 

  13. Chambon P (1996) A decade of molecular biology of retinoic acid receptors. FASEB J 10:940–954

    PubMed  CAS  Google Scholar 

  14. Cinti S (1999) Adipose tissues and obesity. Ital J Anat Embryol 104:37–51

    PubMed  CAS  Google Scholar 

  15. Day CP, James OF (1998) Steatohepatitis: a tale of two "hits"? Gastroenterology 114:842–845

    Article  PubMed  CAS  Google Scholar 

  16. Friedman SL (2003) Liver fibrosis—from bench to bedside. J Hepatol 38(Suppl 1):S38–S53

    Article  PubMed  Google Scholar 

  17. Friedman SL (2008) Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 88:125–172

    Article  PubMed  CAS  Google Scholar 

  18. Galic S, Oakhill JS, Steinberg GR (2010) Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316:129–139

    Article  PubMed  CAS  Google Scholar 

  19. Galli A, Crabb DW, Ceni E, Salzano R, Mello T, Svegliati-Baroni G, Ridolfi F, Trozzi L, Surrenti C, Casini A (2002) Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. Gastroenterology 122:1924–1940

    Article  PubMed  CAS  Google Scholar 

  20. Geerts A (2004) On the origin of stellate cells: mesodermal, endodermal or neuro-ectodermal? J Hepatol 40:331–334

    Article  PubMed  Google Scholar 

  21. Gesta S, Tseng YH, Kahn CR (2007) Developmental origin of fat: tracking obesity to its source. Cell 131:242–256

    Article  PubMed  CAS  Google Scholar 

  22. Green H, Meuth M (1974) An established pre-adipose cell line and its differentiation in culture. Cell 3:127–133

    Article  PubMed  CAS  Google Scholar 

  23. Green H, Kehinde O (1976) Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells. Cell 7:105–113

    Article  PubMed  CAS  Google Scholar 

  24. Harrison EH (2005) Mechanisms of digestion and absorption of dietary vitamin A. Annu Rev Nutr 25:87–103

    Article  PubMed  CAS  Google Scholar 

  25. Horie S, Kitamura Y, Kawasaki H, Terada T (2000) Inhibitory effects of antisense oligonucleotides on the expression of procollagen type III gene in mouse hepatic stellate cells transformed by simian virus 40. Pathol Int 50:937–944

    Article  PubMed  CAS  Google Scholar 

  26. Hui AY, Friedman SL (2003) Molecular basis of hepatic fibrosis. Expert Rev Mol Med 5:1–23

    Article  PubMed  Google Scholar 

  27. Ikejima K, Okumura K, Kon K, Takei Y, Sato N (2007) Role of adipocytokines in hepatic fibrogenesis. J Gastroenterol Hepatol 22:S87–S92

    Article  PubMed  CAS  Google Scholar 

  28. Iredale JP (2001) Hepatic stellate cell behavior during resolution of liver injury. Semin Liver Dis 21:427–436

    Article  PubMed  CAS  Google Scholar 

  29. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556

    Article  PubMed  CAS  Google Scholar 

  30. Kimmel AR, Brasaemle DL, McAndrews-Hill M, Sztalryd C, Londos C (2010) Adoption of perilipin as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins. J Lipid Res 51:468–471

    Article  PubMed  CAS  Google Scholar 

  31. Lee TF, Mak KM, Rackovsky O, Lin YL, Kwong AJ, Loke JC, Friedman SL (2010) Downregulation of hepatic stellate cell activation by retinol and palmitate mediated by adipose differentiation-related protein (ADRP). J Cell Physiol 223:648–657

    PubMed  CAS  Google Scholar 

  32. Londos C, Brasaemle DL, Schultz CJ, Segrest JP, Kimmel AR (1999) Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin Cell Dev Biol 10:51–58

    Article  PubMed  CAS  Google Scholar 

  33. Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM (1990) Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 345:224–229

    Article  PubMed  CAS  Google Scholar 

  34. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839

    Article  PubMed  CAS  Google Scholar 

  35. Marra F, Efsen E, Romanelli RG, Caligiuri A, Pastacaldi S, Batignani G, Bonacchi A, Caporale R, Laffi G, Pinzani M, Gentilini P (2000) Ligands of peroxisome proliferator-activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells. Gastroenterology 119:466–478

    Article  PubMed  CAS  Google Scholar 

  36. Marra F, Bertolani C (2009) Adipokines in liver diseases. Hepatology 50:957–969

    Article  PubMed  CAS  Google Scholar 

  37. McCollum EV, Davis M (1913) The necessity of certain lipins in the diet during growth. J Biol Chem 15:167–175

    CAS  Google Scholar 

  38. McCollum EV, Davis M (1915) The essential factors in the diet during growth. J Biol Chem 23:231–246

    CAS  Google Scholar 

  39. Melton AC, Yee HF (2007) Hepatic stellate cell protrusions couple platelet-derived growth factor-BB to chemotaxis. Hepatology 45:1446–1453

    Article  PubMed  CAS  Google Scholar 

  40. Miyahara T, Schrum L, Rippe R, Xiong S, Yee HF Jr, Motomura K, Anania FA, Willson TM, Tsukamoto H (2000) Peroxisome proliferator-activated receptors and hepatic stellate cell activation. J Biol Chem 275:35715–35722

    Article  PubMed  CAS  Google Scholar 

  41. Moriwaki H, Blaner WS, Piantedosi R, Goodman DS (1988) Effects of dietary retinoid and triglyceride on the lipid composition of rat liver stellate cells and stellate cell lipid droplets. J Lipid Res 29:1523–1534

    PubMed  CAS  Google Scholar 

  42. Morrison RF, Farmer SR (2000) Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 130:3116S–3121S

    PubMed  CAS  Google Scholar 

  43. Nagy NE, Holven KB, Roos N, Senoo H, Kojima N, Norum KR, Blomhoff R (1997) Storage of vitamin A in extrahepatic stellate cells in normal rats. J Lipid Res 38:645–658

    PubMed  CAS  Google Scholar 

  44. Negrel R, Grimaldi P, Ailhaud G (1978) Establishment of preadipocyte clonal line from epididymal fat pad of ob/ob mouse that responds to insulin and to lipolytic hormones. Proc Natl Acad Sci USA 75:6054–6058

    Article  PubMed  CAS  Google Scholar 

  45. Ohta Y, Takenaga M, Tokura Y, Hamaguchi A, Matsumoto T, Kano K, Mugishima H, Okano H, Igarashi R (2008) Mature adipocyte-derived cells, dedifferentiated fat cells (DFAT), promoted functional recovery from spinal cord injury-induced motor dysfunction in rats. Cell Transplant 17:877–886

    Article  PubMed  Google Scholar 

  46. Park KW, Halperin DS, Tontonoz P (2008) Before they were fat: adipocyte progenitors. Cell Metab 8:454–457

    Article  PubMed  CAS  Google Scholar 

  47. Petkovich M, Brand NJ, Krust A, Chambon P (1987) A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330:444–450

    Article  PubMed  CAS  Google Scholar 

  48. Poulos SP, Dodson MV, Hausman GJ (2010) Cell line models for differentiation: preadipocytes and adipocytes. Exp Biol Med (Maywood) 235:1185–1193

    Article  CAS  Google Scholar 

  49. Poulos SP, Hausman DB, Hausman GJ (2010) The development and endocrine functions of adipose tissue. Mol Cell Endocrinol 323:20–34

    Article  PubMed  CAS  Google Scholar 

  50. Redonnet A, Ferrand C, Bairras C, Higueret P, Noel-Suberville C, Cassand P, Atgié C (2008) Synergic effect of vitamin A and high-fat diet in adipose tissue development and nuclear receptor expression in young rats. Br J Nutr 100:722–730

    Article  PubMed  CAS  Google Scholar 

  51. Reynaert H, Thompson MG, Thomas T, Geerts A (2002) Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension. Gut 50:571–581

    Article  PubMed  CAS  Google Scholar 

  52. Ross AC (2007) Vitamin A supplementation and retinoic acid treatment in the regulation of antibody responses in vivo. Vitam Horm 75:197–222

    Article  PubMed  CAS  Google Scholar 

  53. Sauvant P, Abergel A, Partier A, Alexandre-Gouabau MC, Rock E, Sion B, Motta C, Sapin V, Azais-Bresco V (2002) Treatment of the rat hepatic stellate cell line, PAV-1, by retinol and palmitic acid leads to a convenient model to study retinoids metabolism. Biol Cell 94:401–408

    Article  PubMed  CAS  Google Scholar 

  54. Sauvant P, Sapin V, Abergel A, Schmidt CK, Blanchon L, Alexandre-Gouabau MC, Rosenbaum J, Bommelaer G, Rock E, Dastugue B, Nau H, Azais-Braesco V (2002) PAV-1, a new rat hepatic stellate cell line converts retinol into retinoic acid, a process altered by ethanol. Int J Biochem Cell Biol 34:1017–1029

    Article  PubMed  CAS  Google Scholar 

  55. Senoo H, Kojima N, Sato M (2007) Vitamin A-storing cells (stellate cells). Vitam Horm 75:131–159

    Article  PubMed  CAS  Google Scholar 

  56. She H, Xiong S, Hazra S, Tsukamoto H (2005) Adipogenic transcriptional regulation of hepatic stellate cells. J Biol Chem 280:4959–4967

    Article  PubMed  CAS  Google Scholar 

  57. Shen W, Wang Z, Punyanita M, Lei J, Sinav A, Kral JG, Imielinska C, Ross R, Heymsfield SB (2003) Adipose tissue quantification by imaging methods: a proposed classification. Obes Res 11:5–16

    Article  PubMed  Google Scholar 

  58. Soon RK Jr, Yee HF Jr (2008) Stellate cell contraction: role, regulation, and potential therapeutic target. Clin Liver Dis 12:791–803

    Article  PubMed  Google Scholar 

  59. Spiegelman BM, Choy L, Hotamisligil GS, Graves RA, Tontonoz P (1993) Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes. J Biol Chem 268:6823–6826

    PubMed  CAS  Google Scholar 

  60. Straub BK, Stoeffel P, Heid H, Zimbelmann R, Schirmacher P (2008) Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology 47:1936–1946

    Article  PubMed  CAS  Google Scholar 

  61. Suskind DL, Muench MO (2004) Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver: CD34+ cytokeratin 7/8+ cells express markers for stellate cells. J Hepatol 40:261–268

    Article  PubMed  CAS  Google Scholar 

  62. Tansey JT, Sztalryd C, Hlavin EM, Kimmel AR, Londos C (2004) The central role of perilipin a in lipid metabolism and adipocyte lipolysis. IUBMB Life 56:379–385

    Article  PubMed  CAS  Google Scholar 

  63. Theodosiou M, Laudet V, Schubert M (2010) From carrot to clinic: an overview of the retinoic acid signaling pathway. Cell Mol Life Sci 67:1423–1445

    Article  PubMed  CAS  Google Scholar 

  64. Trujillo ME, Scherer PE (2006) Adipose tissue-derived factors: impact on health and disease. Endocr Rev 27:762–778

    PubMed  CAS  Google Scholar 

  65. Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Jarvinen H, Svegliati-Baroni G (2010) From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis 42:320–330

    Article  PubMed  CAS  Google Scholar 

  66. Villarroya F, Giralt M, Iglesias R (1999) Retinoids and adipose tissues: metabolism, cell differentiation and gene expression. Int J Obes Relat Metab Disord 23:1–6

    Article  PubMed  CAS  Google Scholar 

  67. Vogel S, Piantedosi R, Frank J, Lalazar A, Rockey DC, Friedman SL, Blaner WS (2000) An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro. J Lipid Res 41:882–893

    PubMed  CAS  Google Scholar 

  68. Wake K (1971) "Sternzellen" in the liver: perisinusoidal cells with special reference to storage of vitamin A. Am J Anat 132:429–462

    Article  PubMed  CAS  Google Scholar 

  69. Wake K (1980) Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 66:303–353

    Article  PubMed  CAS  Google Scholar 

  70. Wald G (1968) Molecular basis of visual excitation. Science 162:230–239

    Article  PubMed  CAS  Google Scholar 

  71. Weill FX, Blazejewski S, Blanc JF, Huet S, Gauthier JM, Neaud V, Olaso E, Dubuisson L, Azais-Braesco V, Vidal-Vanaclocha F, Balabaud C, Bioulac-Sage P, Rosenbaum J (1997) Characterization of a new human liver myofibroblast cell line: transcriptional regulation of plasminogen activator inhibitor type I by transforming growth factor beta 1. Lab Invest 77:63–70

    PubMed  CAS  Google Scholar 

  72. Weiner FR, Shah A, Smith PJ, Rubin CS, Zern MA (1989) Regulation of collagen gene expression in 3T3-L1 cells. Effects of adipocyte differentiation and tumor necrosis factor alpha. Biochemistry 28:4094–4099

    Article  PubMed  CAS  Google Scholar 

  73. Wolf G (1996) A history of vitamin A and retinoids. FASEB J 10:1102–1107

    PubMed  CAS  Google Scholar 

  74. Wolins NE, Brasaemle DL, Bickel PE (2006) A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett 580:5484–5491

    Article  PubMed  CAS  Google Scholar 

  75. Xu L, Hui AY, Albanis E, Arthur MJ, O'Byrne SM, Blaner WS, Mukherjee P, Friedman SL, Eng FJ (2005) Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut 54:142–151

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work is supported in part by Communauté de Travail des Pyrénées (Région Aquitaine). This review was presented at the 7th Meeting of CTP Network in Pamplona, Navarra Spain on November 17, 2010. Special thanks to Russell Wallace for his kind help with English language.

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  1. UMR 5248 CBMN “Chimie et Biologie des Membranes et des Nanoobjets”, CNRS, Université de Bordeaux, Institut Polytechnique de Bordeaux (IPB), Allée Geoffroy de St Hilaire, Pessac, 33 600, Bordeaux, France

    Patrick Sauvant, Maud Cansell & Claude Atgié

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Sauvant, P., Cansell, M. & Atgié, C. Vitamin A and lipid metabolism: relationship between hepatic stellate cells (HSCs) and adipocytes. J Physiol Biochem 67, 487–496 (2011). https://doi.org/10.1007/s13105-011-0101-7

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