Retinoids: Potent regulators of metabolism

BioFactors

Volumn 39, Issue 2, 2013, Pages 151-163

  Brun, Pierre Jacques ^a   Yang, Kryscilla Jian Zhang ^a   Lee, Seung Ah ^a   Yuen, Jason J ^a   Blaner, William S ^a  

^a Columbia University ^*  (United States)

Author keywords

Adipose tissue; Glucose; Metabolic disease; Pancreas; Vitamin A

Indexed keywords

RETINOIC ACID; RETINOID; RETINOID X RECEPTOR; RETINOL;

ADIPOCYTE; ADIPOGENESIS; ENDOCRINE FUNCTION; FATTY LIVER; GENETIC REGULATION; HUMAN; INSULIN RELEASE; INSULIN SENSITIVITY; ISOMER; LIPID LIVER LEVEL; LIPID METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; VITAMIN INTAKE; VITAMIN METABOLISM; WHITE ADIPOSE TISSUE;

ADIPOSE TISSUE; ANIMALS; GLUCOSE; HUMANS; METABOLIC DISEASES; RETINOIDS; VITAMIN A;

EID: 84876452139     PISSN: 09516433     EISSN: 18728081     Source Type: Journal    
DOI: 10.1002/biof.1056     Document Type: Review

References (101)

1. Goodman, D. S. ( 1984) Vitamin A and retinoids in health and disease. N. Engl. J. Med. 310, 1023-1031.
2. Goodman, D. S. ( 1980) Vitamin A metabolism. Fed. Proc. 39, 2716-2722.
3. Wald, G. ( 1968) Molecular basis of visual excitation. Science 162, 230-239.
4. Balmer, J. E. and Blomhoff, R. ( 2002) Gene expression regulation by retinoic acid. J. Lipid Res. 43, 1773-1808.
5. Chambon, P. ( 1996) A decade of molecular biology of retinoic acid receptors. FASEB J. 10, 940-954.
6. Mangelsdorf, D. J., Umesono, K., and Evans, R. M. ( 1994) The retinoid receptors. In The Retinoids, Biology, Chemistry and Medicine, 2nd edn. ( Sporn, M. B., Roberts, A. B., and Goodman, D. S., eds.). Raven Press Ltd, New York. pp 319-349.
7. Weng, W., Li, L., van Bennekum, A. M., Potter, S. H., Harrison, E. H., et al. ( 1999) Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase knockout mice. Biochemistry 38, 4143-4149.
8. Gilham, D., Labonte, E. D., Rojas, J. C., Jandacek, R. J., Howles, P. N., et al. ( 2007) Carboxyl ester lipase deficiency exacerbates dietary lipid absorption abnormalities and resistance to diet-induced obesity in pancreatic triglyceride lipase knockout mice. J. Biol. Chem. 282, 24642-24649.
9. O'Byrne, S. M., Wongsiriroj, N., Libien, J., Vogel, S., Goldberg, I. J., et al. ( 2005) Retinoid absorption and storage is impaired in mice lacking lecithin:retinol acyltransferase (LRAT). J. Biol. Chem. 280, 35647-35657.
10. Wongsiriroj, N., Piantedosi, R., Palczewski, K., Goldberg, I. J., Johnston, T. P., et al. ( 2008) The molecular basis of retinoid absorption: a genetic dissection. J. Biol. Chem. 283, 13510-13519.
11. Lietz, G., Lange, J., and Rimbach, G. ( 2010) Molecular and dietary regulation of beta, beta-carotene 15, 15′-monooxygenase 1 (BCMO1). Arch. Biochem. Biophys. 502, 8-16.
12. Herr, F. M., Wardlaw, S. A., Kakkad, B., Albrecht, A., Quick, T. C., et al. ( 1993) Intestinal vitamin A metabolism: coordinate distribution of enzymes and CRBP(II). J. Lipid Res. 34, 1545-1554.
13. Blaner, W. S., Obunike, J. C., Kurlandsky, S. B., al-Haideri, M., Piantedosi, R., et al. ( 1994) Lipoprotein lipase hydrolysis of retinyl ester. Possible implications for retinoid uptake by cells. J. Biol. Chem. 269, 16559-16565.
14. Cooper, A. D. ( 1997) Hepatic uptake of chylomicron remnants. J. Lipid Res. 38, 2173-2192.
15. Yu, K. C. and Cooper, A. D. ( 2001) Postprandial lipoproteins and atherosclerosis. Front. Biosci. 6, D332-D354.
16. Shirakami, Y., Lee, S. A., Clugston, R. D., and Blaner, W. S. ( 2012) Hepatic metabolism of retinoids and disease associations. Biochim. Biophys. Acta 1821, 124-136.
17. D'Ambrosio, D. N., Clugston, R. D., and Blaner, W. S. ( 2011) Vitamin A metabolism: an update. Nutrients 3, 63-103.
18. Kastner, P., Mark, M., Ghyselinck, N., Krezel, W., Dupe, V., et al. ( 1997) Genetic evidence that the retinoid signal is transduced by heterodimeric RXR/RAR functional units during mouse development. Development 124, 313-326.
19. Lee, M. S., Kliewer, S. A., Provencal, J., Wright, P. E., and Evans, R. M. ( 1993) Structure of the retinoid X receptor alpha DNA binding domain: a helix required for homodimeric DNA binding. Science 260, 1117-1121.
20. Schwabe, J. W., Chapman, L., Finch, J. T., and Rhodes, D. ( 1993) The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements. Cell 75, 567-578.
21. Glass, C. K. and Rosenfeld, M. G. ( 2000) The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 14, 121-141.
22. Wurtz, J. M., Bourguet, W., Renaud, J. P., Vivat, V., Chambon, P., et al. ( 1996) A canonical structure for the ligand-binding domain of nuclear receptors. Nat. Struct. Biol. 3, 206.
23. Mangelsdorf, D. J. and Evans, R. M. ( 1995) The RXR heterodimers and orphan receptors. Cell 83, 841-850.
24. Bastien, J. and Rochette-Egly, C. ( 2004) Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene 328, 1-16.
25. Kubo, Y., Wada, M., Ohba, T., and Takahashi, N. ( 2005) Formation of retinoylated proteins from retinoyl-CoA in rat tissues. J. Biochem. 138, 493-500.
26. Pingitore, A., Cione, E., Senatore, V., and Genchi, G. ( 2009) Adrenal glands and testes as steroidogenic tissue are affected by retinoylation reaction. J. Bioenerg. Biomembr. 41, 215-221.
27. Takahashi, N. and Fujiu, Y. ( 2010) Cytokeratins 16 and 10 bind to retinoic acid covalently in skin tissue of mice. Br. J. Dermatol. 162, 974-979.
28. Pipkin, J. L., Hinson, W., Lyn-Cook, L. E., Duffy, P. H., Feuers, R. J., et al. ( 1996) The effect of aging and dietary restriction on the retinoylation of nuclear matrix proteins in rats. Aging 8, 263-270.
29. Cione, E., Pingitore, A., Perri, M., and Genchi, G. ( 2009) Influence of all-trans-retinoic acid on oxoglutarate carrier via retinoylation reaction. Biochim. Biophys. Acta 1791, 3-7.
30. Schallreuter, K. U., Janner, M., Mensing, H., Breitbart, E. W., Berger, J., et al. ( 1991) Thioredoxin reductase activity at the surface of human primary cutaneous melanomas and their surrounding skin. Int. J. Cancer 48, 15-19.
31. Takahashi, N., Liapi, C., Anderson, W. B., and Breitman, T. R. ( 1991) Retinoylation of the cAMP-binding regulatory subunits of type I and type II cAMP-dependent protein kinases in HL60 cells. Arch. Biochem. Biophys. 290, 293-302.
32. Takahashi, N. and Breitman, T. R. ( 1992) The covalent labeling of proteins by 17 beta-estradiol, retinoic acid, and progesterone in the human breast cancer cell lines MCF-7 and MCF-7/AdrR. J. Steroid Biochem. Mol. Biol. 43, 489-497.
33. Tournier, S., Raynaud, F., Gerbaud, P., Lohmann, S. M., Anderson, W. B., et al. ( 1996) Retinoylation of the type II cAMP-binding regulatory subunit of cAMP-dependent protein kinase is increased in psoriatic human fibroblasts. J. Cell. Physiol. 167, 196-203.
34. Takahashi, N. and Breitman, T. R. ( 1994) Retinoylation of vimentin in the human myeloid leukemia cell line HL60. J. Biol. Chem. 269, 5913-5917.
35. Takahashi, N. and Breitman, T. R. ( 1991) Retinoylation of proteins in leukemia, embryonal carcinoma, and normal kidney cell lines: differences associated with differential responses to retinoic acid. Arch. Biochem. Biophys. 285, 105-110.
36. Takahashi, N. and Ohba, T. ( 2009) Demonstration of basic proteins that bind retinoic acid in the human myeloid leukemia cell line HL60. Biol. Pharm. Bull. 32, 1943-1946.
37. Zhang, X. K. ( 2007) Targeting Nur77 translocation. Expert Opin. Ther. Targets 11, 69-79.
38. Cao, X., Liu, W., Lin, F., Li, H., Kolluri, S. K., et al. ( 2004) Retinoid X receptor regulates Nur77/TR3-dependent apoptosis corrected by modulating its nuclear export and mitochondrial targeting. Mol. Cell. Biol. 24, 9705-9725.
39. Tsutsumi, C., Okuno, M., Tannous, L., Piantedosi, R., Allan, M., et al. ( 1992) Retinoids and retinoid-binding protein expression in rat adipocytes. J. Biol. Chem. 267, 1805-1810.
40. van Bennekum, A. M., Kako, Y., Weinstock, P. H., Harrison, E. H., Deckelbaum, R. J., et al. ( 1999) Lipoprotein lipase expression level influences tissue clearance of chylomicron retinyl ester. J. Lipid Res. 40, 565-574.
41. Lobo, G. P., Amengual, J., Li, H. N., Golczak, M., Bonet, M. L., et al. ( 2010) Beta, beta-carotene decreases peroxisome proliferator receptor gamma activity and reduces lipid storage capacity of adipocytes in a beta, beta-carotene oxygenase 1-dependent manner. J. Biol. Chem. 285, 27891-27899.
42. Bonet, M. L., Ribot, J., Felipe, F., and Palou, A. ( 2003) Vitamin A and the regulation of fat reserves. Cell. Mol. Life Sci. 60, 1311-1321.
43. Wei, S., Lai, K., Patel, S., Piantedosi, R., Shen, H., et al. ( 1997) Retinyl ester hydrolysis and retinol efflux from BFC-1beta adipocytes. J. Biol. Chem. 272, 14159-14165.
44. Strom, K., Gundersen, T. E., Hansson, O., Lucas, S., Fernandez, C., et al. ( 2009) Hormone-sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL. FASEB J. 23, 2307-2316.
45. Jeyakumar, S. M., Vajreswari, A., and Giridharan, N. V. ( 2008) Vitamin A regulates obesity in WNIN/Ob obese rat; independent of stearoyl-CoA desaturase-1. Biochem. Biophys. Res. Commun. 370, 243-247.
46. Jeyakumar, S. M., Vajreswari, A., Sesikeran, B., and Giridharan, N. V. ( 2005) Vitamin A supplementation induces adipose tissue loss through apoptosis in lean but not in obese rats of the WNIN/Ob strain. J. Mol. Endocrinol. 35, 391-398.
47. Felipe, F., Mercader, J., Ribot, J., Palou, A., and Bonet, M. L. ( 2005) Effects of retinoic acid administration and dietary vitamin A supplementation on leptin expression in mice: lack of correlation with changes of adipose tissue mass and food intake. Biochim. Biophys. Acta 1740, 258-265.
48. Ribot, J., Felipe, F., Bonet, M. L., and Palou, A. ( 2001) Changes of adiposity in response to vitamin A status correlate with changes of PPAR gamma 2 expression. Obes. Res. 9, 500-509.
49. Sagazio, A., Piantedosi, R., Alba, M., Blaner, W. S., and Salvatori, R. ( 2007) Vitamin A deficiency does not influence longitudinal growth in mice. Nutrition 23, 483-488.
50. Mercader, J., Ribot, J., Murano, I., Felipe, F., Cinti, S., et al. ( 2006) Remodeling of white adipose tissue after retinoic acid administration in mice. Endocrinology 147, 5325-5332.
51. Berry, D. C., Soltanian, H., and Noy, N. ( 2010) Repression of cellular retinoic acid-binding protein II during adipocyte differentiation. J. Biol. Chem. 285, 15324-15332.
52. Kane, M. A., Folias, A. E., and Napoli, J. L. ( 2008) HPLC/UV quantitation of retinal, retinol, and retinyl esters in serum and tissues. Anal. Biochem. 378, 71-79.
53. Berry, D. C. and Noy, N. ( 2009) All-trans-retinoic acid represses obesity and insulin resistance by activating both peroxisome proliferation-activated receptor beta/delta and retinoic acid receptor. Mol. Cell. Biol. 29, 3286-3296.
54. Suryawan, A. and Hu, C. Y. ( 1997) Effect of retinoic acid on differentiation of cultured pig preadipocytes. J. Anim. Sci. 75, 112-117.
55. Xue, J. C., Schwarz, E. J., Chawla, A., and Lazar, M. A. ( 1996) Distinct stages in adipogenesis revealed by retinoid inhibition of differentiation after induction of PPARgamma. Mol. Cell. Biol. 16, 1567-1575.
56. Schwarz, E. J., Reginato, M. J., Shao, D., Krakow, S. L., and Lazar, M. A. ( 1997) Retinoic acid blocks adipogenesis by inhibiting C/EBP beta-mediated transcription. Mol. Cell. Biol. 17, 1552-1561.
57. Shaw, N., Elholm, M., and Noy, N. ( 2003) Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta. J. Biol. Chem. 278, 41589-41592.
58. Rieck, M., Meissner, W., Ries, S., Muller-Brusselbach, S., and Muller, R. ( 2008) Ligand-mediated regulation of peroxisome proliferator-activated receptor (PPAR) beta/delta: a comparative analysis of PPAR-selective agonists and all-trans retinoic acid. Mol. Pharmacol. 74, 1269-1277.
59. Borland, M. G., Foreman, J. E., Girroir, E. E., Zolfaghari, R., Sharma, A. K., et al. ( 2008) Ligand activation of peroxisome proliferator-activated receptor-beta/delta inhibits cell proliferation in human HaCaT keratinocytes. Mol. Pharmacol. 74, 1429-1442.
60. Berry, D. C., Desantis, D., Soltanian, H., Croniger, C. M., and Noy, N. ( 2012) Retinoic acid upregulates preadipocyte genes to block adipogenesis and suppress diet-induced obesity. Diabetes 61, 1112-1121.
61. Ziouzenkova, O., Orasanu, G., Sharlach, M., Akiyama, T. E., Berger, J. P., et al. ( 2007) Retinaldehyde represses adipogenesis and diet-induced obesity. Nat. Med. 13, 695-702.
62. Kiefer, F. W., Vernochet, C., O'Brien, P., Spoerl, S., Brown, J. D., et al. ( 2012) Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue. Nat. Med. 18, 918-925.
63. Yang, Q., Graham, T. E., Mody, N., Preitner, F., Peroni, O. D., et al. ( 2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436, 356-362.
64. Aeberli, I., Biebinger, R., Lehmann, R., L'Allemand, D., Spinas, G. A., et al. ( 2007) Serum retinol-binding protein 4 concentration and its ratio to serum retinol are associated with obesity and metabolic syndrome components in children. J. Clin. Endocrinol. Metab. 92, 4359-4365.
65. Kotnik, P., Fischer-Posovszky, P., and Wabitsch, M. ( 2011) RBP4: a controversial adipokine. Eur. J. Endocrinol. 165, 703-711.
66. Berry, D. C., Jin, H., Majumdar, A., and Noy, N. ( 2011) Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses. Proc. Natl. Acad. Sci. USA 108, 4340-4345.
67. Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., et al. ( 2007) A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 315, 820-825.
68. Norseen, J., Hosooka, T., Hammarstedt, A., Yore, M. M., Kant, S., et al. ( 2012) Retinol-binding protein 4 inhibits insulin signaling in adipocytes by inducing proinflammatory cytokines in macrophages through a c-Jun N-terminal kinase- and toll-like receptor 4-dependent and retinol-independent mechanism. Mol. Cell. Biol. 32, 2010-2019.
69. Kato, M., Kato, K., Blaner, W. S., Chertow, B. S., and Goodman, D. S. ( 1985) Plasma and cellular retinoid-binding proteins and transthyretin (prealbumin) are all localized in the islets of Langerhans in the rat. Proc. Natl. Acad. Sci. USA 82, 2488-2492.
70. Chertow, B. S., Blaner, W. S., Baranetsky, N. G., Sivitz, W. I., Cordle, M. B., et al. ( 1987) Effects of vitamin A deficiency and repletion on rat insulin secretion in vivo and in vitro from isolated islets. J. Clin. Invest. 79, 163-169.
71. Chertow, B. S., Webb, M. D., Leidy, J. W., Jr., and Cordle, M. B. ( 1989) Protective effects of retinyl palmitate on streptozotocin- and alloxan-induced beta cell toxicity and diabetes in the rat. Res. Commun. Chem. Pathol. Pharmacol. 63, 27-44.
72. Chertow, B. S., Moore, M. R., Blaner, W. S., Wilford, M. R., and Cordle, M. B. ( 1989) Cytoplasmic retinoid-binding proteins and retinoid effects on insulin release in RINm5F beta-cells. Diabetes 38, 1544-1548.
73. Fernandez-Mejia, C. and Davidson, M. B. ( 1992) Regulation of glucokinase and proinsulin gene expression and insulin secretion in RIN-m5F cells by dexamethasone, retinoic acid, and thyroid hormone. Endocrinology 130, 1660-1668.
74. Cabrera-Valladares, G., German, M. S., Matschinsky, F. M., Wang, J., and Fernandez-Mejia, C. ( 1999) Effect of retinoic acid on glucokinase activity and gene expression and on insulin secretion in primary cultures of pancreatic islets. Endocrinology 140, 3091-3096.
75. Chertow, B. S., Driscoll, H. K., Primerano, D. A., Cordle, M. B., and Matthews, K. A. ( 1996) Retinoic acid receptor transcripts and effects of retinol and retinoic acid on glucagon secretion from rat islets and glucagon-secreting cell lines. Metabolism 45, 300-305.
76. Chertow, B. S., Blaner, W. S., Rajan, N., Primerano, D. A., Meda, P., et al. ( 1993) Retinoic acid receptor, cytosolic retinol-binding and retinoic acid-binding protein mRNA transcripts and proteins in rat insulin-secreting cells. Diabetes 42, 1109-1114.
77. Kutlu, B., Burdick, D., Baxter, D., Rasschaert, J., Flamez, D., et al. ( 2009) Detailed transcriptome atlas of the pancreatic beta cell. BMC Med. Genomics 2, 3.
78. Chertow, B. S., Driscoll, H. K., Goking, N. Q., Primerano, D., Cordle, M. B., et al. ( 1997) Retinoid-X receptors and the effects of 9-cis-retinoic acid on insulin secretion from RINm5F cells. Metabolism 46, 656-660.
79. Clark, A. R., Wilson, M. E., London, N. J., James, R. F., and Docherty, K. ( 1995) Identification and characterization of a functional retinoic acid/thyroid hormone-response element upstream of the human insulin gene enhancer. Biochem. J. 309 ( Part 3), 863-870.
80. Blumentrath, J., Neye, H., and Verspohl, E. J. ( 2001) Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS-1 cells. Cell Biochem. Funct. 19, 159-169.
81. Chertow, B. S., Goking, N. Q., Driscoll, H. K., Primerano, D. A., and Matthews, K. A. ( 1997) Effects of all-trans-retinoic acid (ATRA) and retinoic acid receptor (RAR) expression on secretion, growth, and apoptosis of insulin-secreting RINm5F cells. Pancreas 15, 122-131.
82. Chertow, B. S., Driscoll, H. K., Blaner, W. S., Meda, P., Cordle, M. B., et al. ( 1994) Effects of vitamin A deficiency and repletion on rat glucagon secretion. Pancreas 9, 475-484.
83. Kane, M. A., Folias, A. E., Pingitore, A., Perri, M., Obrochta, K. M., et al. ( 2010) Identification of 9-cis-retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion. Proc. Natl. Acad. Sci. USA 107, 21884-21889.
84. Miyazaki, S., Taniguchi, H., Moritoh, Y., Tashiro, F., Yamamoto, T., et al. ( 2010) Nuclear hormone retinoid X receptor (RXR) negatively regulates the glucose-stimulated insulin secretion of pancreatic ss-cells. Diabetes 59, 2854-2861.
85. Ravnskjaer, K., Boergesen, M., Rubi, B., Larsen, J. K., Nielsen, T., et al. ( 2005) Peroxisome proliferator-activated receptor alpha (PPARalpha) potentiates, whereas PPARgamma attenuates, glucose-stimulated insulin secretion in pancreatic beta-cells. Endocrinology 146, 3266-3276.
86. Shiota, G. ( 2007) Role of retinoic acid receptor in steatohepatitis-related tumor formation. J. Gastroenterol. Hepatol. 22 ( Suppl 1), S101-S107.
87. Kang, H. W., Bhimidi, G. R., Odom, D. P., Brun, P. J., Fernandez, M. L., et al. ( 2007) Altered lipid catabolism in the vitamin A deficient liver. Mol. Cell. Endocrinol. 271, 18-27.
88. Kane, M. A. ( 2012) Analysis, occurrence, and function of 9-cis-retinoic acid. Biochim. Biophys. Acta 1821, 10-20.
89. Jain, R. and Lammert, E. ( 2009) Cell-cell interactions in the endocrine pancreas. Diabetes Obes. Metab. 11 ( Suppl 4), 159-167.
90. Sima, A., Parisotto, M., Mader, S., and Bhat, P. V. ( 2009) Kinetic characterization of recombinant mouse retinal dehydrogenase types 3 and 4 for retinal substrates. Biochim. Biophys. Acta 1790, 1660-1664.
91. Shimamura, M., Karasawa, H., Sakakibara, S., and Shinagawa, A. ( 2010) Raldh3 expression in diabetic islets reciprocally regulates secretion of insulin and glucagon from pancreatic islets. Biochem. Biophys. Res. Commun. 401, 79-84.
92. Kane, M. A., Folias, A. E., Pingitore, A., Perri, M., Krois, C. R., et al. ( 2011) CrbpI modulates glucose homeostasis and pancreas 9-cis-retinoic acid concentrations. Mol. Cell. Biol. 31, 3277-3285.
93. Zizola, C. F., Frey, S. K., Jitngarmkusol, S., Kadereit, B., Yan, N., et al. ( 2010) Cellular retinol-binding protein type I (CRBP-I) regulates adipogenesis. Mol. Cell. Biol. 30, 3412-3420.
94. Suano de Souza, F. I., Silverio Amancio, O. M., Saccardo Sarni, R. O., Sacchi Pitta, T., Fernandes, A. P., et al. ( 2008) Non-alcoholic fatty liver disease in overweight children and its relationship with retinol serum levels. Int. J. Vitam. Nutr. Res. 78, 27-32.
95. Musso, G., Gambino, R., De Michieli, F., Biroli, G., Premoli, A., et al. ( 2007) Nitrosative stress predicts the presence and severity of nonalcoholic fatty liver at different stages of the development of insulin resistance and metabolic syndrome: possible role of vitamin A intake. Am. J. Clin. Nutr. 86, 661-671.
96. Villaca Chaves, G., Pereira, S. E., Saboya, C. J., and Ramalho, A. ( 2008) Non-alcoholic fatty liver disease and its relationship with the nutritional status of vitamin A in individuals with class III obesity. Obes. Surg. 18, 378-385.
97. Oliveros, L. B., Domeniconi, M. A., Vega, V. A., Gatica, L. V., Brigada, A. M., et al. ( 2007) Vitamin A deficiency modifies lipid metabolism in rat liver. Br. J. Nutr. 97, 263-272.
98. McClintick, J. N., Crabb, D. W., Tian, H., Pinaire, J., Smith, J. R., et al. ( 2006) Global effects of vitamin A deficiency on gene expression in rat liver: evidence for hypoandrogenism. J. Nutr. Biochem. 17, 345-355.
99. Amengual, J., Ribot, J., Bonet, M. L., and Palou, A. ( 2010) Retinoic acid treatment enhances lipid oxidation and inhibits lipid biosynthesis capacities in the liver of mice. Cell. Physiol. Biochem. 25, 657-666.
100. Mukhopadhyay, B., Liu, J., Osei-Hyiaman, D., Godlewski, G., Mukhopadhyay, P., et al. ( 2010) Transcriptional regulation of cannabinoid receptor-1 expression in the liver by retinoic acid acting via retinoic acid receptor-gamma. J. Biol. Chem. 285, 19002-19011.
101. Lenhard, J. M., Lancaster, M. E., Paulik, M. A., Weiel, J. E., Binz, J. G., et al. ( 1999) The RXR agonist LG100268 causes hepatomegaly, improves glycaemic control and decreases cardiovascular risk and cachexia in diabetic mice suffering from pancreatic beta-cell dysfunction. Diabetologia 42, 545-554.