In recent years, the importance of vitamin A in adipose tissue biology, obesity and type II diabetes has become apparent. This review focuses on recent developments within the area of vitamin A and adipose tissue biology. Adipose tissue has an active vitamin A metabolism as it not only stores vitamin A but retinol is also converted to its active metabolite retinoic acid. Several mouse models point to a relationship between vitamin A metabolism and the development of adiposity. Similarly, in vitro studies provide new molecular mechanisms for the function of different forms of vitamin A and retinol- or retinoic acid-binding proteins in adipose tissue.
References
[1]
Kurlandsky, S.B.; Gamble, M.V.; Ramakrishnan, R.; Blaner, W.S. Plasma delivery of retinoic acid to tissues in the rat. J. Biol. Chem.?1995, 270, 17850–17857.
[2]
Gallego, O.; Belyaeva, O.V.; Porte, S.; Ruiz, F.X.; Stetsenko, A.V.; Shabrova, E.V.; Kostereva, N.V.; Farres, J.; Pares, X.; Kedishvili, N.Y. Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases and aldo-keto reductases with retinoids. Biochem. J.?2006, 399, 101–109.
[3]
Pares, X.; Farres, J.; Kedishvili, N.; Duester, G. Medium- and short-chain dehydrogenase/reductase gene and protein families: Medium-chain and short-chain dehydrogenases/reductases in retinoid metabolism. Cell Mol. Life Sci.?2008, 65, 3936–3949.
[4]
Duester, G.; Mic, F.A.; Molotkov, A. Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid. Chem. Biol. Interact.?2003, 143–144, 201–210.
[5]
Ziouzenkova, O.; Plutzky, J. Retinoid metabolism and nuclear receptor responses: New insights into coordinated regulation of the PPAR-RXR complex. FEBS Lett.?2008, 582, 32–38.
[6]
Balmer, J.E.; Blomhoff, R. Gene expression regulation by retinoic acid. J. Lipid Res.?2002, 43, 1773–1808.
Vogel, S.; Gamble, M.; Blaner, W.S. Biosynthesis, Absorption, Metabolism, and Transport of Retinoids. In Retinoids: The Biochemical and Molecular Basis for Vitamin A and Retinoid Action; Nau, H., Blaner, W.S., Eds.; Springer-Verlag: Berlin, Germany, 1999; Volume 139, pp. 31–95.
[9]
Blaner, W.S.; Olson, J.A. Retinol and retinoic acid metabolism. In The Retinoids: Biology, Chemistry and Medicine; Sporn, M.B., Roberts, A.B., Goodman, D.S., Eds.; Raven Press: New York, NY, USA, 1994; pp. 229–255.
[10]
Duncan, R.E.; Ahmadian, M.; Jaworski, K.; Sarkadi-Nagy, E.; Sul, H.S. Regulation of lipolysis in adipocytes. Annu. Rev. Nutr.?2007, 27, 79–101.
[11]
Frayn, K.N.; Arner, P.; Yki-Jarvinen, H. Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem.?2006, 42, 89–103.
[12]
Kahn, B.B.; Flier, J.S. Obesity and insulin resistance. J. Clin. Invest.?2000, 106, 473–481.
[13]
Rosen, E.D.; Spiegelman, B.M. Adipocytes as regulators of energy balance and glucose homeostasis. Nature?2006, 444, 847–853.
Hessel, S.; Eichinger, A.; Isken, A.; Amengual, J.; Hunzelmann, S.; Hoeller, U.; Elste, V.; Hunziker, W.; Goralczyk, R.; Oberhauser, V.; von Lintig, J.; Wyss, A. CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice. J. Biol. Chem.?2007, 282, 33553–33561.
[16]
Lobo, G.P.; Amengual, J.; Li, H.N.; Golczak, M.; Bonet, M.L.; Palczewski, K.; von Lintig, J. 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.?2010, 285, 27891–27899.
[17]
Tsutsumi, C.; Okuno, M.; Tannous, L.; Piantedosi, R.; Allan, M.; Goodman, D.S.; Blaner, W.S. Retinoids and retinoid-binding protein expression in rat adipocytes. J. Biol. Chem.?1992, 267, 1805–1810.
[18]
Liu, L.; Gudas, L.J. Disruption of the lecithin:retinol acyltransferase gene makes mice more susceptible to vitamin A deficiency. J. Biol. Chem.?2005, 280, 40226–40234.
[19]
O’Byrne, S.M.; Wongsiriroj, N.; Libien, J.; Vogel, S.; Goldberg, I.J.; Baehr, W.; Palczewski, K.; Blaner, W.S. Retinoid absorption and storage is impaired in mice lacking lecithin:retinol acyltransferase (LRAT). J. Biol. Chem.?2005, 280, 35647–35657.
[20]
Liu, L.; Tang, X.H.; Gudas, L.J. Homeostasis of retinol in lecithin:retinol acyltransferase gene knockout mice fed a high retinol diet. Biochem. Pharmacol.?2008, 75, 2316–2324.
[21]
Randolph, R.K.; Winkler, K.E.; Ross, A.C. Fatty acyl CoA-dependent and -independent retinol esterification by rat liver and lactating mammary gland microsomes. Arch. Biochem. Biophys.?1991, 288, 500–508.
[22]
Ross, A.C.; Kempner, E.S. Radiation inactivation analysis of acyl-CoA:retinol acyltransferase and lecithin:retinol acyltransferase in rat liver. J. Lipid Res.?1993, 34, 1201–1207.
[23]
Yen, C.L.; Monetti, M.; Burri, B.J.; Farese, R.V., Jr. The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. J. Lipid Res.?2005, 46, 1502–1511.
Ong, D.E.; Newcomer, M.E.; Chytil, F. Cellular retinoid-binding proteins. In The Retinoids, Biology, Chemistry, and Medicine, 2nd; Sporn, M.B., Roberts, A.B., Goodman, D.S., Eds.; Raven Press: New York, NY, USA, 1994; pp. 283–317.
[28]
Ross, A.C. Cellular metabolism and activation of retinoids: Roles of cellular retinoid-binding proteins. FASEB J.?1993, 7, 317–327.
[29]
Napoli, J.L. A gene knockout corroborates the integral function of cellular retinol-binding protein in retinoid metabolism. Nutr. Rev.?2000, 58, 230–236.
[30]
Noy, N. Retinoid-binding proteins: Mediators of retinoid action. Biochem. J.?2000, 348, 481–495.
[31]
Piantedosi, R.; Ghyselinck, N.; Blaner, W.S.; Vogel, S. Cellular retinol-binding protein type III is needed for retinoid incorporation into milk. J. Biol. Chem.?2005, 280, 24286–24292.
[32]
Vogel, S.; Mendelsohn, C.L.; Mertz, J.; Piantedosi, R.; Waldburger, C.; Gottesman, M.E.; Blaner, W.S. Characterization of a new member of the fatty acid-binding protein family that binds all-trans-retinol. J. Biol. Chem.?2001, 276, 1353–1360.
[33]
Ghyselinck, N.B.; Bavik, C.; Sapin, V.; Mark, M.; Bonnies, D.; Hindelang, C.; Dierich, A.; Nilsson, C.B.; Hakansson, H.; Sauvant, P.; Azais-Braesco, V.; Frasson, M.; Picaud, S.; Chambon, P. Cellular retinol-binding protein I is essential for vitamin A homeostasis. EMBO J.?1999, 18, 4903–4914.
[34]
Matt, N.; Schmidt, C.K.; Dupe, V.; Dennefeld, C.; Nau, H.; Chambon, P.; Mark, M.; Ghyselinck, N.B. Contribution of cellular retinol-binding protein type 1 to retinol metabolism during mouse development. Dev. Dyn.?2005, 233, 167–176.
[35]
Caprioli, A.; Zhu, H.; Sato, T. CRBP-III:lacZ expression pattern reveals a novel heterogeneity of vascular endothelial cells. Genesis?2004, 40, 139–145.
[36]
Jeyakumar, S.M.; Vajreswari, A.; Giridharan, N.V. Vitamin A regulates obesity in WNIN/Ob obese rat; independent of stearoyl-CoA desaturase-1. Biochem. Biophys. Res. Commun.?2008, 370, 243–247.
[37]
Felipe, F.; Mercader, J.; Ribot, J.; Palou, A.; Bonet, M.L. 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?2005, 1740, 258–265.
[38]
Berry, D.C.; Noy, N. 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.?2009, 29, 3286–3296.
[39]
Mercader, J.; Ribot, J.; Murano, I.; Felipe, F.; Cinti, S.; Bonet, M.L.; Palou, A. Remodeling of white adipose tissue after retinoic acid administration in mice. Endocrinology?2006, 147, 5325–5332.
[40]
Ribot, J.; Felipe, F.; Bonet, M.L.; Palou, A. Changes of adiposity in response to vitamin A status correlate with changes of PPAR gamma 2 expression. Obes. Res.?2001, 9, 500–509.
[41]
Felipe, F.; Bonet, M.L.; Ribot, J.; Palou, A. Modulation of resistin expression by retinoic acid and vitamin A status. Diabetes?2004, 53, 882–889.
[42]
Zhang, M.; Hu, P.; Krois, C.R.; Kane, M.A.; Napoli, J.L. Altered vitamin A homeostasis and increased size and adiposity in the rdh1-null mouse. FASEB J.?2007, 21, 2886–2896.
[43]
Miyoshi, H.; Perfield, J.W.; Souza, S.C.; Shen, W.J.; Zhang, H.H.; Stancheva, Z.S.; Kraemer, F.B.; Obin, M.S.; Greenberg, A.S. Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes. J. Biol. Chem.?2007, 282, 996–1002.
[44]
Paik, J.; During, A.; Harrison, E.H.; Mendelsohn, C.L.; Lai, K.; Blaner, W.S. Expression and characterization of a murine enzyme able to cleave beta-carotene. The formation of retinoids. J. Biol. Chem.?2001, 276, 32160–32168.
[45]
Redmond, T.M.; Gentleman, S.; Duncan, T.; Yu, S.; Wiggert, B.; Gantt, E.; Cunningham, F.X., Jr. Identification, expression, and substrate specificity of a mammalian beta-carotene 15,15'-dioxygenase. J. Biol. Chem.?2001, 276, 6560–6565.
[46]
Zizola, C.F.; Frey, S.K.; Jitngarmkusol, S.; Kadereit, B.; Yan, N.; Vogel, S. Cellular retinol?binding protein type I (CRBP-I) regulates adipogenesis. Mol. Cell. Biol.?2010, 30, 3412–3420.
[47]
Zizola, C.F.; Schwartz, G.J.; Vogel, S. Cellular retinol-binding protein type III is a PPARgamma target gene and plays a role in lipid metabolism. Am. J. Physiol. Endocrinol. Metab.?2008, 295, E1358–E1368.
[48]
Yang, Q.; Graham, T.E.; Mody, N.; Preitner, F.; Peroni, O.D.; Zabolotny, J.M.; Kotani, K.; Quadro, L.; Kahn, B.B. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature?2005, 436, 356–362.
[49]
Ziegelmeier, M.; Bachmann, A.; Seeger, J.; Lossner, U.; Kratzsch, J.; Bluher, M.; Stumvoll, M.; Fasshauer, M. Serum levels of adipokine retinol-binding protein-4 in relation to renal function. Diabetes Care?2007, 30, 2588–2592.
[50]
Graham, T.E.; Yang, Q.; Bluher, M.; Hammarstedt, A.; Ciaraldi, T.P.; Henry, R.R.; Wason, C.J.; Oberbach, A.; Jansson, P.A.; Smith, U.; Kahn, B.B. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N. Engl. J. Med.?2006, 354, 2552–2563.
[51]
Graham, T.E.; Wason, C.J.; Bluher, M.; Kahn, B.B. Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects. Diabetologia?2007, 50, 814–823.
[52]
Aeberli, I.; Biebinger, R.; Lehmann, R.; L’Allemand, D.; Spinas, G.A.; Zimmermann, M.B. 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.?2007, 92, 4359–4365.
[53]
Qi, Q.; Yu, Z.; Ye, X.; Zhao, F.; Huang, P.; Hu, F.B.; Franco, O.H.; Wang, J.; Li, H.; Liu, Y.; Lin, X. Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people. J. Clin. Endocrinol. Metab.?2007, 92, 4827–4834.
[54]
Broch, M.; Vendrell, J.; Ricart, W.; Richart, C.; Fernandez-Real, J.M. Circulating retinol-binding protein-4, insulin sensitivity, insulin secretion, and insulin disposition index in obese and nonobese subjects. Diabetes Care?2007, 30, 1802–1806.
[55]
Lewis, J.G.; Shand, B.I.; Frampton, C.M.; Elder, P.A.; Scott, R.S. Plasma retinol-binding protein is not a marker of insulin resistance in overweight subjects: A three year longitudinal study. Clin. Biochem.?2008, 41, 1034–1038.
[56]
Von Eynatten, M.; Lepper, P.M.; Liu, D.; Lang, K.; Baumann, M.; Nawroth, P.P.; Bierhaus, A.; Dugi, K.A.; Heemann, U.; Allolio, B.; Humpert, P.M. Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease. J. Clin. Endocrinol. Metab.?2007, 50, 1930–1937.
[57]
Lewis, J.G.; Shand, B.I.; Frampton, C.M.; Elder, P.A. An ELISA for plasma retinol-binding protein using monoclonal and polyclonal antibodies: Plasma variation in normal and insulin resistant subjects. Clin. Biochem.?2007, 40, 828–834.
[58]
Henze, A.; Frey, S.K.; Raila, J.; Tepel, M.; Scholze, A.; Pfeiffer, A.F.; Weickert, M.O.; Spranger, J.; Schweigert, F.J. Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels. Diabetes?2008, 57, 3323–3326. 18796616
[59]
Janke, J.; Engeli, S.; Boschmann, M.; Adams, F.; Bohnke, J.; Luft, F.C.; Sharma, A.M.; Jordan, J. Retinol-binding protein 4 in human obesity. Diabetes?2006, 55, 2805–2810.
[60]
Rosen, E.D.; MacDougald, O.A. Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol.?2006, 7, 885–896.
Berry, D.C.; Soltanian, H.; Noy, N. Repression of cellular retinoic acid-binding protein II during adipocyte differentiation. J. Biol. Chem.?2010, 285, 15324–15332.
[63]
Chawla, A.; Schwarz, E.J.; Dimaculangan, D.D.; Lazar, M.A. Peroxisome proliferator-activated receptor (PPAR) gamma: Adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology?1994, 135, 798–800.
[64]
Moon, H.S.; Guo, D.D.; Song, H.H.; Kim, I.Y.; Jiang, H.L.; Kim, Y.K.; Chung, C.S.; Choi, Y.J.; Lee, H.G.; Cho, C.S. Regulation of adipocyte differentiation by PEGylated all-trans retinoic acid: Reduced cytotoxicity and attenuated lipid accumulation. J. Nutr. Biochem.?2007, 18, 322–331.
[65]
Suryawan, A.; Hu, C.Y. Effect of retinoic acid on differentiation of cultured pig preadipocytes. J. Anim. Sci.?1997, 75, 112–117.
Shao, D.; Lazar, M.A. Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation. J. Biol. Chem.?1997, 272, 21473–21478.
[68]
Xue, J.C.; Schwarz, E.J.; Chawla, A.; Lazar, M.A. Distinct stages in adipogenesis revealed by retinoid inhibition of differentiation after induction of PPARgamma. Mol. Cell. Biol.?1996, 16, 1567–1575.
[69]
Schupp, M.; Lefterova, M.I.; Janke, J.; Leitner, K.; Cristancho, A.G.; Mullican, S.E.; Qatanani, M.; Szwergold, N.; Steger, D.J.; Curtin, J.C.; Kim, R.J.; Suh, M.; Albert, M.R.; Engeli, S.; Gudas, L.J.; Lazar, M.A. Retinol saturase promotes adipogenesis and is downregulated in obesity. Proc. Natl. Acad. Sci. USA?2009, 106, 1105–1110.