LXRβ is the dominant LXR subtype in skeletal muscle regulating lipogenesis and cholesterol efflux

American Journal of Physiology - Endocrinology and Metabolism

Volumn 298, Issue 3, 2010, Pages

  Hessvik, N P ^a   Boekschoten, M V ^b,c   Baltzersen, M A ^a   Kersten, S ^b,c   Xu, X ^d   Andersen H ^d   Rustan, A C ^a   Thoresen, G H ^a  

^a UNIVERSITY OF OSLO   (Norway)

^b WAGENINGEN UNIVERSITY   (Netherlands)

^c TOP INSTITUTE FOOD AND NUTRITION   (Netherlands)

^d ASTRAZENECA R AND D   (Sweden)

Author keywords

Intramyocellular lipids; Lipid metabolism; Liver X receptor; Myotubes; Nuclear receptors

Indexed keywords

APOLIPOPROTEIN A1; CHOLESTEROL; GLUCOSE; LIVER X RECEPTOR; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA; MESSENGER RNA; N (2,2,2 TRIFLUOROETHYL) N [4 [2,2,2 TRIFLUORO 1 HYDROXY 1 (TRIFLUOROMETHOXY)ETHYL]PHENYL]BENZENESULFONAMIDE;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CHOLESTEROL METABOLISM; CONTROLLED STUDY; EMBRYO; FEMALE; GENE EXPRESSION; GENE TARGETING; GENETIC ANALYSIS; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; KNOCKOUT MOUSE; LIPID METABOLISM; LIPOGENESIS; MALE; MICROARRAY ANALYSIS; MOUSE; MYOTUBE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SKELETAL MUSCLE; TISSUE CULTURE; WILD TYPE;

ANIMALS; CELLS, CULTURED; CHOLESTEROL; FEEDBACK, PHYSIOLOGICAL; LIPID METABOLISM; LIPOGENESIS; MICE; MICE, KNOCKOUT; MUSCLE, SKELETAL; MYOBLASTS; ORPHAN NUCLEAR RECEPTORS;

EID: 77349106414     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00553.2009     Document Type: Article

References (57)

1. Adams JM 2nd, Pratipanawatr T, Berria R, Wang E, DeFronzo RA, Sullards MC, Mandarino LJ. Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 53: 25-31, 2004.
2. Alberti S, Schuster G, Parini P, Feltkamp D, Diczfalusy U, Rudling M, Angelin B, Bjorkhem I, Pettersson S, Gustafsson JA. Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice. J Clin Invest 107: 565-573, 2001.
3. Boden G. Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver. Curr Diab Rep 6: 177-181, 2006.
4. Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV. The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. N Engl J Med 328: 238-244, 1993.
5. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254, 1976.
6. Bradley MN, Hong C, Chen M, Joseph SB, Wilpitz DC, Wang X, Lusis AJ, Collins A, Hseuh WA, Collins JL, Tangirala RK, Tontonoz P. Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE. J Clin Invest 117: 2337-2346, 2007.
7. Cao G, Liang Y, Broderick CL, Oldham BA, Beyer TP, Schmidt RJ, Zhang Y, Stayrook KR, Suen C, Otto KA, Miller AR, Dai J, Foxworthy P, Gao H, Ryan TP, Jiang XC, Burris TP, Eacho PI, Etgen GJ. Antidiabetic action of a liver X receptor agonist mediated by inhibition of hepatic gluconeogenesis. J Biol Chem 278: 1131-1136, 2003.
8. Cozzone D, Debard C, Dif N, Ricard N, Disse E, Vouillarmet J, Rabasa-Lhoret R, Laville M, Pruneau D, Rieusset J, Lefai E, Vidal H. Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells. Diabetologia 49: 990-999, 2006.
9. Dahlquist KD, Salomonis N, Vranizan K, Lawlor SC, Conklin BR. GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet 31: 19-20, 2002.
10. Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, Bunney WE, Myers RM, Speed TP, Akil H, Watson SJ, Meng F. Evolving gene/ transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res 33: e175, 2005.
11. Ellis BA, Poynten A, Lowy AJ, Furler SM, Chisholm DJ, Kraegen EW, Cooney GJ. Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle. Am J Physiol Endocrinol Metab 279: E554-E560, 2000.
12. Gaster M, Rustan AC, Aas V, Beck-Nielsen H. Reduced lipid oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin: evidence from cultured myotubes. Diabetes 53: 542-548, 2004.
13. Grefhorst A, Elzinga BM, Voshol PJ, Plosch T, Kok T, Bloks VW, van der Sluijs FH, Havekes LM, Romijn JA, Verkade HJ, Kuipers F. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J Biol Chem 277: 34182-34190, 2002.
14. Grefhorst A, van Dijk TH, Hammer A, van der Sluijs FH, Havinga R, Havekes LM, Romijn JA, Groot PH, Reijngoud DJ, Kuipers F. Differential effects of pharmacological liver X receptor activation on hepatic and peripheral insulin sensitivity in lean and ob/ob mice. Am J Physiol Endocrinol Metab 289: E829-E838, 2005.
15. Hayden MR, Clee SM, Brooks-Wilson A, Genest J, Jr, Attie A, Kastelein JJ. Cholesterol efflux regulatory protein, Tangier disease and familial high-density lipoprotein deficiency. Curr Opin Lipidol 11: 117-122, 2000.
16. Houck KA, Borchert KM, Hepler CD, Thomas JS, Bramlett KS, Michael LF, Burris TP. T0901317 is a dual LXR/FXR agonist. Mol Genet Metab 83: 184-187, 2004.
17. Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51: 2005-2011, 2002.
18. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383: 728-731, 1996.
19. Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28: 27-30, 2000.
20. Kase ET, Andersen B, Nebb HI, Rustan AC, Hege Thoresen G. 22-Hydroxycholesterols regulate lipid metabolism differently than T0901317 in human myotubes. Biochim Biophys Acta 1761: 1515-1522, 2006.
21. Kase ET, Thoresen GH, Westerlund S, Hojlund K, Rustan AC, Gaster M. Liver X receptor antagonist reduces lipid formation and increases glucose metabolism in myotubes from lean, obese and type 2 diabetic individuals. Diabetologia 50: 2171-2180, 2007.
22. Kase ET, Wensaas AJ, Aas V, Hojlund K, Levin K, Thoresen GH, Beck-Nielsen H, Rustan AC, Gaster M. Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway. Diabetes 54: 1108-1115, 2005.
23. Korach-André M, Parini P, Larsson L, Arner A, Steffensen KR, Gustafsson JA. Separate and overlapping metabolic functions of LXRα and LXRβ in C57Bl/6 female mice. Am J Physiol Endocrinol Metab 298: E167-E178, 2010.
24. Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O, Bain J, Stevens R, Dyck JRB, Newgard CB, Lopaschuk GD, Muoio DM. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance [see comment]. Cell Metab 7: 45-56, 2008.
25. Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, Castrillo A, Wilpitz DC, Mangelsdorf DJ, Collins JL, Saez E, Tontonoz P. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci USA 100: 5419-5424, 2003.
26. Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH. Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Invest 117: 1679-1689, 2007.
27. Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 307: 384-387, 2005.
28. Lu TT, Repa JJ, Mangelsdorf DJ. Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism. J Biol Chem 276: 37735-37738, 2001.
29. Lund EG, Menke JG, Sparrow CP. Liver X receptor agonists as potential therapeutic agents for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol 23: 1169-1177, 2003.
30. Lund EG, Peterson LB, Adams AD, Lam MHN, Burton CA, Chin J, Guo Q, Huang S, Latham M, Lopez JC, Menke JG, Milot DP, Mitnaul LJ, Rex-Rabe SE, Rosa RL, Tian JY, Wright SD, Sparrow CP. Different roles of liver X receptor alpha and beta in lipid metabolism: effects of an alpha-selective and a dual agonist in mice deficient in each subtype. Biochem Pharmacol 71: 453-463, 2006.
31. Manco M, Mingrone G, Greco AV, Capristo E, Gniuli D, De Gaetano A, Gasbarrini G. Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides. Metab Clin Exp 49: 220-224, 2000.
32. Mitro N, Vargas L, Romeo R, Koder A, Saez E. T0901317 is a potent PXR ligand: implications for the biology ascribed to LXR. FEBS Lett 581: 1721-1726, 2007.
33. Muscat GEO, Wagner BL, Hou J, Tangirala RK, Bischoff ED, Rohde P, Petrowski M, Li J, Shao G, Macondray G, Schulman IG. Regulation of cholesterol homeostasis and lipid metabolism in skeletal muscle by liver X receptors. J Biol Chem 277: 40722-40728, 2002.
34. Nomiyama T, Bruemmer D. Liver X receptors as therapeutic targets in metabolism and atherosclerosis. Curr Atheroscler Rep 10: 88-95, 2008.
35. Oram JF, Lawn RM. ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J Lipid Res 42: 1173-1179, 2001.
36. Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlien LH. Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46: 983-988, 1997.
37. Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 93: 693-704, 1998.
38. Peter A, Weigert C, Staiger H, Rittig K, Cegan A, Lutz P, Machicao F, Haring HU, Schleicher E. Induction of stearoyl-CoA desaturase protects human arterial endothelial cells against lipotoxicity. Am J Physiol Endocrinol Metab 295: E339-E349, 2008.
39. Quinet EM, Savio DA, Halpern AR, Chen L, Schuster GU, Gustafsson JA, Basso MD, Nambi P. Liver X receptor (LXR)-beta regulation in LXRalpha-deficient mice: implications for therapeutic targeting. Mol Pharmacol 70: 1340-1349, 2006.
40. Rando TA, Blau HM. Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. J Cell Biol 125: 1275-1287, 1994.
41. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 14: 2819-2830, 2000.
42. Sartor MA, Tomlinson CR, Wesselkamper SC, Sivaganesan S, Leikauf GD, Medvedovic M. Intensity-based hierarchical Bayes method improves testing for differentially expressed genes in microarray experiments. BMC Bioinformatics 7: 538, 2006.
43. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S, Wang S, Thoolen M, Mangelsdorf DJ, Lustig KD, Shan B. Role of LXRs in control of lipogenesis. Genes Dev 14: 2831-2838, 2000.
44. Schuster GU, Parini P, Wang L, Alberti S, Steffensen KR, Hansson GK, Angelin B, Gustafsson JA. Accumulation of foam cells in liver X receptor-deficient mice. Circulation 106: 1147-1153, 2002.
45. Skrede S, Bremer J, Berge RK, Rustan AC. Stimulation of fatty acid oxidation by a 3-thia fatty acid reduces triacylglycerol secretion in cultured rat hepatocytes. J Lipid Res 35: 1395-1404, 1994.
46. Steffensen KR, Nilsson M, Schuster GU, Stulnig TM, Dahlman-Wright K, Gustafsson JA. Gene expression profiling in adipose tissue indicates different transcriptional mechanisms of liver X receptors alpha and beta, respectively. Biochem Biophys Res Commun 310: 589-593, 2003.
47. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.[see comment]. Proc Natl Acad Sci USA 102: 15545-15550, 2005.
48. Teboul M, Enmark E, Li Q, Wikstrom AC, Pelto-Huikko M, Gustafsson JA. OR-1, a member of the nuclear receptor superfamily that interacts with the 9-cis-retinoic acid receptor. Proc Natl Acad Sci USA 92: 2096-2100, 1995.
49. Terasaka N, Hiroshima A, Koieyama T, Ubukata N, Morikawa Y, Nakai D, Inaba T. T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice [see comment]. FEBS Lett 536: 6-11, 2003.
50. Tontonoz P, Mangelsdorf DJ. Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol 17: 985-993, 2003.
51. Virkamaki A, Korsheninnikova E, Seppala-Lindroos A, Vehkavaara S, Goto T, Halavaara J, Hakkinen AM, Yki-Jarvinen H. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes 50: 2337-2343, 2001.
52. Wang H, Zhang Y, Yehuda-Shnaidman E, Medvedev AV, Kumar N, Daniel KW, Robidoux J, Czech MP, Mangelsdorf DJ, Collins S. Liver X receptor alpha is a transcriptional repressor of the uncoupling protein 1 gene and the brown fat phenotype. Mol Cell Biol 28: 2187-2200, 2008.
53. Wang Y, Rogers PM, Su C, Varga G, Stayrook KR, Burris TP. Regulation of cholesterologenesis by the oxysterol receptor, LXRα. J Biol Chem 283: 26332-26339, 2008.
54. Wensaas AJ, Rustan AC, Lovstedt K, Kull B, Wikstrom S, Drevon CA, Hallen S. Cell-based multiwell assays for the detection of substrate accumulation and oxidation. J Lipid Res 48: 961-967, 2007.
55. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev 9: 1033-1045, 1995.
56. Wu Z, Irizarry RA, Gentleman R, Martinez-Murillo F, Spencer F. A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc 99: 909-917, 2004.
57. Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest 116: 607-614, 2006.