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Gene Review

Chol1  -  cholesterol 1

Mus musculus

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Disease relevance of Chol1


Psychiatry related information on Chol1


High impact information on Chol1

  • Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI [10].
  • Finally, because of the organizing potential of cholesterol in membranes, disturbances in cellular cholesterol transport have implications for a wide variety of human diseases, of which selected examples are given [11].
  • Metabolites elevated in individuals with the metabolic syndrome and diabetes destabilize ABCA1 protein and decrease cholesterol export from macrophages [12].
  • One of these factors is ATP-binding cassette transporter A1 (ABCA1), a cell membrane protein that mediates the transport of cholesterol, phospholipids, and other metabolites from cells to lipid-depleted HDL apolipoproteins [12].
  • The high-affinity receptor state requires both Mg(2+) and cholesterol, which probably function as allosteric modulators [13].

Chemical compound and disease context of Chol1


Biological context of Chol1


Anatomical context of Chol1


Associations of Chol1 with chemical compounds

  • Thus, the mRNA levels of genes involved in fatty acid and cholesterol synthesis are rapidly (<1 h) repressed by leptin administration, in association with an acute decrease in plasma insulin levels and decreased sterol regulator element-binding protein-1 expression [18].
  • In addition, taurocholenic acid greatly increased incorporation of labeled glucose into hepatic cholesterol in obese or non-obese mice fed either diet [24].
  • Effect of delta22-5beta-taurocholenic acid on hepatic cholesterol and fatty acid in gold thioglucose obese mice fed low- or high-fat diets [24].
  • Cholesterol levels were significantly elevated in both male and female homozygous carriers of the Chol1/NZO allele [4].
  • T exerts proatherogenic effects on macrophage function by facilitating the uptake of modified lipoproteins and an antiatherogenic effect by stimulating efflux of cellular cholesterol to HDL [19].

Physical interactions of Chol1

  • Hepatobiliary cholesterol transport is not impaired in Abca1-null mice lacking HDL [25].
  • The plant sterol diosgenin has been shown to stimulate biliary cholesterol secretion in mice without affecting the expression of the adenosine triphosphate-binding cassette transporter heterodimer Abcg5/g8 [26].
  • In the present study we hypothesized that cholesteryl ester is transported from caveolae through the cytosol to an internal membrane by a caveolin chaperone complex similar to the one we originally described for the transport of newly synthesized cholesterol [27].
  • Thus, we suggest that SgIII directly binds to cholesterol components of the SGM and targets CgA to SGs in pituitary and pancreatic endocrine cells [28].
  • ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice [29].

Enzymatic interactions of Chol1


Co-localisations of Chol1

  • Caspase3 whole mount immunostaining revealed that cholesterol biosynthesis colocalizes with apoptotic regions that are targets of the morphogenic signal Sonic hedgehog [34].

Regulatory relationships of Chol1


Other interactions of Chol1


Analytical, diagnostic and therapeutic context of Chol1


  1. Leptin promotes biliary cholesterol elimination during weight loss in ob/ob mice by regulating the enterohepatic circulation of bile salts. Hyogo, H., Roy, S., Paigen, B., Cohen, D.E. J. Biol. Chem. (2002) [Pubmed]
  2. Leptin induces the hepatic high density lipoprotein receptor scavenger receptor B type I (SR-BI) but not cholesterol 7alpha-hydroxylase (Cyp7a1) in leptin-deficient (ob/ob) mice. Lundåsen, T., Liao, W., Angelin, B., Rudling, M. J. Biol. Chem. (2003) [Pubmed]
  3. Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha. Li, J., Bosch-Marce, M., Nanayakkara, A., Savransky, V., Fried, S.K., Semenza, G.L., Polotsky, V.Y. Physiol. Genomics (2006) [Pubmed]
  4. Diet-dependent obesity and hypercholesterolemia in the New Zealand obese mouse: identification of a quantitative trait locus for elevated serum cholesterol on the distal mouse chromosome 5. Giesen, K., Plum, L., Kluge, R., Ortlepp, J., Joost, H.G. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  5. 7-Dehydrocholesterol-dependent proteolysis of HMG-CoA reductase suppresses sterol biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH syndrome. Fitzky, B.U., Moebius, F.F., Asaoka, H., Waage-Baudet, H., Xu, L., Xu, G., Maeda, N., Kluckman, K., Hiller, S., Yu, H., Batta, A.K., Shefer, S., Chen, T., Salen, G., Sulik, K., Simoni, R.D., Ness, G.C., Glossmann, H., Patel, S.B., Tint, G.S. J. Clin. Invest. (2001) [Pubmed]
  6. Neuronal membrane cholesterol loss enhances amyloid peptide generation. Abad-Rodriguez, J., Ledesma, M.D., Craessaerts, K., Perga, S., Medina, M., Delacourte, A., Dingwall, C., De Strooper, B., Dotti, C.G. J. Cell Biol. (2004) [Pubmed]
  7. Different susceptibilities to the formation of cholesterol gallstones in mice. Alexander, M., Portman, O.W. Hepatology (1987) [Pubmed]
  8. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1. Beulens, J.W., Sierksma, A., van Tol, A., Fournier, N., van Gent, T., Paul, J.L., Hendriks, H.F. J. Lipid Res. (2004) [Pubmed]
  9. Dietary modification of high density lipoprotein phospholipid and influence on cellular cholesterol efflux. Gillotte, K.L., Lund-Katz, S., de la Llera-Moya, M., Parks, J.S., Rudel, L.L., Rothblat, G.H., Phillips, M.C. J. Lipid Res. (1998) [Pubmed]
  10. Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI. Krieger, M. Annu. Rev. Biochem. (1999) [Pubmed]
  11. Mechanisms for cellular cholesterol transport: defects and human disease. Ikonen, E. Physiol. Rev. (2006) [Pubmed]
  12. ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Oram, J.F., Heinecke, J.W. Physiol. Rev. (2005) [Pubmed]
  13. The oxytocin receptor system: structure, function, and regulation. Gimpl, G., Fahrenholz, F. Physiol. Rev. (2001) [Pubmed]
  14. Ciliary neurotrophic factor improves diabetic parameters and hepatic steatosis and increases basal metabolic rate in db/db mice. Sleeman, M.W., Garcia, K., Liu, R., Murray, J.D., Malinova, L., Moncrieffe, M., Yancopoulos, G.D., Wiegand, S.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  15. Glucose-dependent regulation of cholesterol ester metabolism in macrophages by insulin and leptin. O'Rourke, L., Gronning, L.M., Yeaman, S.J., Shepherd, P.R. J. Biol. Chem. (2002) [Pubmed]
  16. Initiation of hyperinsulinemia and hyperleptinemia is diet dependent in C57BL/6 mice. Harte, R.A., Kirk, E.A., Rosenfeld, M.E., LeBoeuf, R.C. Horm. Metab. Res. (1999) [Pubmed]
  17. Inherited primary hypothyroidism in mice. Beamer, W.J., Eicher, E.M., Maltais, L.J., Southard, J.L. Science (1981) [Pubmed]
  18. Transcriptional profiling reveals global defects in energy metabolism, lipoprotein, and bile acid synthesis and transport with reversal by leptin treatment in ob/ob mouse liver. Liang, C.P., Tall, A.R. J. Biol. Chem. (2001) [Pubmed]
  19. Androgens and coronary artery disease. Wu, F.C., von Eckardstein, A. Endocr. Rev. (2003) [Pubmed]
  20. A biphasic response of hepatobiliary cholesterol metabolism to dietary fat at the onset of obesity in the mouse. Roy, S., Hyogo, H., Yadav, S.K., Wu, M.K., Jelicks, L.A., Locker, J.D., Frank, P.G., Lisanti, M.P., Silver, D.L., Cohen, D.E. Hepatology (2005) [Pubmed]
  21. Identification of four chromosomal loci determining obesity in a multifactorial mouse model. Warden, C.H., Fisler, J.S., Shoemaker, S.M., Wen, P.Z., Svenson, K.L., Pace, M.J., Lusis, A.J. J. Clin. Invest. (1995) [Pubmed]
  22. Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation. Robertson, K.M., Norgård, M., Windahl, S.H., Hultenby, K., Ohlsson, C., Andersson, G., Gustafsson, J.A. J. Bone Miner. Res. (2006) [Pubmed]
  23. Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Fu, J., Oveisi, F., Gaetani, S., Lin, E., Piomelli, D. Neuropharmacology (2005) [Pubmed]
  24. Effect of delta22-5beta-taurocholenic acid on hepatic cholesterol and fatty acid in gold thioglucose obese mice fed low- or high-fat diets. Jansen, G.R. J. Nutr. Biochem. (1999) [Pubmed]
  25. Hepatobiliary cholesterol transport is not impaired in Abca1-null mice lacking HDL. Groen, A.K., Bloks, V.W., Bandsma, R.H., Ottenhoff, R., Chimini, G., Kuipers, F. J. Clin. Invest. (2001) [Pubmed]
  26. Diosgenin-induced biliary cholesterol secretion in mice requires Abcg8. Kosters, A., Frijters, R.J., Kunne, C., Vink, E., Schneiders, M.S., Schaap, F.G., Nibbering, C.P., Patel, S.B., Groen, A.K. Hepatology (2005) [Pubmed]
  27. Cholesteryl ester is transported from caveolae to internal membranes as part of a caveolin-annexin II lipid-protein complex. Uittenbogaard, A., Everson, W.V., Matveev, S.V., Smart, E.J. J. Biol. Chem. (2002) [Pubmed]
  28. Secretogranin III binds to cholesterol in the secretory granule membrane as an adapter for chromogranin A. Hosaka, M., Suda, M., Sakai, Y., Izumi, T., Watanabe, T., Takeuchi, T. J. Biol. Chem. (2004) [Pubmed]
  29. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Terasaka, N., Miyazaki, A., Kasanuki, N., Ito, K., Ubukata, N., Koieyama, T., Kitayama, K., Tanimoto, T., Maeda, N., Inaba, T. Atherosclerosis (2007) [Pubmed]
  30. Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia. Yagyu, H., Kitamine, T., Osuga, J., Tozawa, R., Chen, Z., Kaji, Y., Oka, T., Perrey, S., Tamura, Y., Ohashi, K., Okazaki, H., Yahagi, N., Shionoiri, F., Iizuka, Y., Harada, K., Shimano, H., Yamashita, H., Gotoda, T., Yamada, N., Ishibashi, S. J. Biol. Chem. (2000) [Pubmed]
  31. PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1. Chui, P.C., Guan, H.P., Lehrke, M., Lazar, M.A. J. Clin. Invest. (2005) [Pubmed]
  32. Oxidized low density lipoprotein suppresses the expression of tumor necrosis factor-alpha mRNA in stimulated murine peritoneal macrophages. Hamilton, T.A., Ma, G.P., Chisolm, G.M. J. Immunol. (1990) [Pubmed]
  33. Possible role of mevalonate in the hypercholesterolemia seen in experimental chronic renal failure. Subang, M.C., Stewart-Phillips, J.L., Pappu, A.S., Subang, R., Gagnon, R.F. Nephron (1995) [Pubmed]
  34. Embryonic expression of cholesterogenic genes is restricted to distinct domains and colocalizes with apoptotic regions in mice. Laubner, D., Breitling, R., Adamski, J. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  35. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. Shimano, H., Horton, J.D., Hammer, R.E., Shimomura, I., Brown, M.S., Goldstein, J.L. J. Clin. Invest. (1996) [Pubmed]
  36. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Maxwell, K.N., Breslow, J.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  37. Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner. Li, Y., Choi, M., Suino, K., Kovach, A., Daugherty, J., Kliewer, S.A., Xu, H.E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  38. Autoregulation of the human liver X receptor alpha promoter. Laffitte, B.A., Joseph, S.B., Walczak, R., Pei, L., Wilpitz, D.C., Collins, J.L., Tontonoz, P. Mol. Cell. Biol. (2001) [Pubmed]
  39. Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice. Harada, K., Shen, W.J., Patel, S., Natu, V., Wang, J., Osuga, J., Ishibashi, S., Kraemer, F.B. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  40. Attenuation of hypercholesterolemia and hyperglycemia in ob/ob mice by NPY Y2 receptor ablation. Naveilhan, P., Svensson, L., Nyström, S., Ekstrand, A.J., Ernfors, P. Peptides (2002) [Pubmed]
  41. Characterization of plasma lipids in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow. Nishina, P.M., Lowe, S., Wang, J., Paigen, B. Metab. Clin. Exp. (1994) [Pubmed]
  42. Reduced cholesterol accumulation by leptin deficient (ob/ob) mouse macrophages. Kjerrulf, M., Berke, Z., Aspegren, A., Umaerus, M., Nilsson, T., Svensson, L., Hurt-Camejo, E. Inflamm. Res. (2006) [Pubmed]
  43. Restoration of gallstone susceptibility by leptin in C57BL/6J ob/ob mice. Hyogo, H., Roy, S., Cohen, D.E. J. Lipid Res. (2003) [Pubmed]
  44. Food restriction normalizes chylomicron remnant metabolism in murine models of obesity as assessed by a novel stable isotope breath test. Martins, I.J., Tran, J.M., Redgrave, T.G. J. Nutr. (2002) [Pubmed]
  45. Evidence that leptin contributes to intestinal cholesterol absorption in obese (ob/ob) mice and wild-type mice. Igel, M., Lindenthal, B., Giesa, U., von, B.K. Lipids (2002) [Pubmed]
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