title: CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice.
abstract: Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% suppression of VLDL output in vivo, and VLDL secretion was reduced in vitro using incubated liver slices. The effect of CD36 deletion was mediated by enhancing formation of hepatic prostaglandins D2, F2, and E2. Treatment of CD36-deficient slices with inhibitors of cyclooxygenases reversed the reduction in triglyceride secretion. We also examined the effect of CD36 deletion on the obesity-associated spontaneous steatosis of the ob/ob mouse that is driven by enhanced de novo lipogenesis. Homozygous ob/ob mice lacking CD36 (ob-CD36⁻/⁻) were generated and studied for hepatic triglyceride accumulation and VLDL secretion. Livers of ob/ob mice were steatotic as expected and had 5-fold more CD36 on Kupffer cells and hepatocytes. CD36 deletion exacerbated the steatosis by impairing hepatic triglyceride and apoB secretion through increasing prostaglandin levels. These findings suggest an unappreciated role of CD36 in regulating VLDL secretion, which might have relevance to some forms of fatty liver. They provide insight into the association reported in humans between CD36 protein expression and serum levels of apoB and VLDL particle number.
authors: Department of Medicine Washington University School of Medicine, St. Louis, MO 63110.
authors: Fatiha
authors: F
authors: Nassir
authors: Okunade L
authors: OL
authors: Adewole
authors: Elizabeth M
authors: EM
authors: Brunt
authors: Nada A
authors: NA
authors: Abumrad
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000172:deficiency* / Q000235:genetics*; D005234:Fatty Liver / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D011453:Prostaglandins / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D008079:Lipoproteins, VLDL; D011453:Prostaglandins
keywords: Kupffer cells; cyclooxygenase; triglyceride
references: Exp Biol Med (Maywood). 2011 Oct;236(10):1116-21
references: 21885479
references: Am J Physiol Gastrointest Liver Physiol. 2010 Oct;299(4):G855-66
references: 20595619
references: Cell Metab. 2012 Feb 8;15(2):240-6
references: 22326225
references: Gastroenterology. 2006 Apr;130(4):1343-6
references: 16618425
references: J Biol Chem. 2008 May 9;283(19):12949-59
references: 18321850
references: Science. 2011 Jun 24;332(6037):1519-23
references: 21700865
references: Metabolism. 2011 Jul;60(7):1001-11
references: 21075404
references: World J Gastroenterol. 2012 May 21;18(19):2300-8
references: 22654421
references: J Biol Chem. 2011 Jul 15;286(28):25201-10
references: 21610069
references: J Biol Chem. 2012 Nov 9;287(46):38901-12
references: 23019328
references: Curr Opin Lipidol. 2001 Apr;12(2):151-7
references: 11264986
references: J Lipid Res. 2002 Jul;43(7):1035-45
references: 12091487
references: Int J Exp Pathol. 2006 Feb;87(1):1-16
references: 16436109
references: Gut. 2011 Oct;60(10):1394-402
references: 21270117
references: Digestion. 2006;74(1):28-32
references: 16988508
references: Gastroenterology. 2008 Feb;134(2):424-31
references: 18242210
references: Trends Endocrinol Metab. 2009 Mar;20(2):72-7
references: 19185504
references: J Lipid Res. 2012 Mar;53(3):561-566
references: 22210925
references: J Surg Res. 2011 Aug;169(2):301-10
references: 20080257
references: Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1281-7
references: 18388185
references: Nutr Metab (Lond). 2010 Apr 27;7:35
references: 20423497
references: Biol Pharm Bull. 2005 Aug;28(8):1418-23
references: 16079486
references: Biochem J. 1989 Aug 15;262(1):195-201
references: 2818563
references: Horm Metab Res. 1994 Feb;26(2):85-7
references: 8200619
references: J Lipid Res. 2001 May;42(5):751-9
references: 11352982
references: J Gastroenterol. 2013 Apr;48(4):434-41
references: 23397118
references: Physiol Rev. 2010 Jan;90(1):23-46
references: 20086073
references: J Clin Invest. 2012 Jun;122(6):2267-82
references: 22546859
references: J Obes. 2013;2013:296537
references: 23401753
references: Biochim Biophys Acta. 2006 Feb;1761(2):160-71
references: 16545597
references: Chem Rev. 2011 Oct 12;111(10):6130-85
references: 21910409
references: J Lipid Res. 1992 Jul;33(7):1017-27
references: 1331281
references: J Clin Invest. 2002 May;109(10):1381-9
references: 12021254
references: J Clin Invest. 2005 May;115(5):1290-7
references: 15841205
references: Br J Pharmacol. 2008 Sep;155(1):4-16
references: 18552881
references: FEBS Lett. 2006 Oct 9;580(23):5484-91
references: 16962104
references: J Biol Chem. 2000 Aug 11;275(32):25023-30
references: 10827200
references: Gastroenterology. 2006 Oct;131(4):1197-207
references: 17030189
references: FASEB J. 2013 Mar;27(3):1191-202
references: 23233532
references: Physiol Rev. 2010 Jan;90(1):367-417
references: 20086080
references: J Lipid Res. 2006 Sep;47(9):2028-41
references: 16790840
references: J Lipid Res. 2009 Apr;50 Suppl:S237-42
references: 19011112
references: Diabetes. 1999 Jan;48(1):121-7
references: 9892232
references: Physiol Rev. 2012 Jul;92(3):1061-85
references: 22811425
references: Cell Tissue Res. 2002 Feb;307(2):173-80
references: 11845324
references: Curr Opin Clin Nutr Metab Care. 2012 Mar;15(2):107-11
references: 22248592
references: Am J Physiol. 1980 Oct;239(4):E265-E268
references: 6999915
references: J Biol Chem. 2003 Jun 13;278(24):21450-8
references: 12670935
references: FEBS Lett. 2010 Jun 3;584(11):2168-75
references: 20347811
references: J Biol Chem. 2011 May 20;286(20):17785-95
references: 21454644
references: Hum Mol Genet. 2011 Jan 1;20(1):193-201
references: 20935172
references: J Clin Invest. 2005 May;115(5):1343-51
references: 15864352
references: Diabetes. 2005 Feb;54(2):472-81
references: 15677505
references: Cell Metab. 2010 Aug 4;12(2):174-86
references: 20674862
references: J Lipid Res. 2010 Jul;51(7):1918-28
references: 20237389
references: Diabetes Metab. 2003 Nov;29(5):478-85
references: 14631324
references: J Lipid Res. 1996 Jan;37(1):210-20
references: 8820116
references: Diabetes. 2007 Dec;56(12):2863-71
references: 17728375
references: Am J Physiol Gastrointest Liver Physiol. 2000 Jul;279(1):G100-6
references: 10898751