title: Fenofibrate increases serum vaspin by upregulating its expression in adipose tissue.
abstract: Fenofibrate is a peroxisome proliferator-activated receptor-α that has been clinically used to treat dyslipidemia and insulin resistance. To better understand the molecular mechanisms underlying fenofibrate action, we investigated whether fenofibrate affects serum levels of vaspin, an adipocytokine that has recently been shown to link obesity and insulin resistance. Fenofibrate treatment significantly increased serum vaspin levels of dyslipidemic patients, which correlated with reduced body weight and increased insulin sensitivity. To elucidate the biochemical mechanisms of fenofibrate action, we investigated the effect of fenofibrate on vaspin mRNA and protein expressions in obese rats. Fenofibrate greatly increased vaspin mRNA and protein levels in visceral adipose tissue consisting of retroperitoneal, mesenteric, and periepididymal adipose tissue but not in the subcutaneous adipose tissue, which correlated with increased serum vaspin levels and increased insulin sensitivity in obese rats. Consistent with a direct effect on vaspin expression, fenofibrate treatment significantly increased the mRNA and protein expression levels of vaspin in 3T3-L1 adipocytes. Together, our results demonstrate for the first time that fenofibrate upregulates vaspin expression in dyslipidemic human subjects and suggest that upregulation of vaspin expression in adipocytes may provide a mechanism by which fenofibrate improves insulin sensitivity in dyslipidemic patients.
authors.affiliation: Institute of Endocrinology & Metabolism, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.forename: Datong
authors.initials: D
authors.lastname: Deng
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Fang
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Honglin
authors.initials: H
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.forename: Youmin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism*; D011345:Fenofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D056128:Obesity, Abdominal / Q000188:drug therapy / Q000378:metabolism*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000097:blood / Q000378:metabolism*; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; C506516:Serpina12 protein, rat; D015843:Serpins; D045162:Thiazolidinediones; D011345:Fenofibrate; D000077205:Pioglitazone
references.citation: Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):635-41
references.pmid: 17194889
references.citation: Drugs. 1997 Oct;54(4):615-33
references.pmid: 9339964
references.citation: Exp Mol Med. 2009 Jun 30;41(6):397-405
references.pmid: 19322024
references.citation: Eur Cytokine Netw. 2011 Dec;22(4):181-6
references.pmid: 22266100
references.citation: Diabetes Res Clin Pract. 2009 Jun;84(3):325-8
references.pmid: 19356820
references.citation: Endocrine. 2012 Jun;41(3):374-83
references.pmid: 22434412
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10610-5
references.pmid: 16030142
references.citation: Eur J Pharmacol. 2008 Jan 28;579(1-3):433-8
references.pmid: 18155694
references.citation: Diabetes. 2008 Feb;57(2):372-7
references.pmid: 17991760
references.citation: Nutrition. 2009 Jul-Aug;25(7-8):818-27
references.pmid: 19268533
references.citation: JAMA. 2001 May 16;285(19):2486-97
references.pmid: 11368702
references.citation: Diabet Med. 1998 Jul;15(7):539-53
references.pmid: 9686693
references.citation: Chin Med J (Engl). 2010 Apr 5;123(7):936-41
references.pmid: 20497691
references.citation: Endocrine. 2012 Apr;41(2):176-82
references.pmid: 22139797
references.citation: Biochem Biophys Res Commun. 2006 Jan 6;339(1):430-6
references.pmid: 16298335
references.citation: Exp Clin Endocrinol Diabetes. 2010 Mar;118(3):184-9
references.pmid: 18726871
references.citation: Diabetologia. 2011 Jul;54(7):1819-23
references.pmid: 21465327
references.citation: Metabolism. 2008 Jul;57(7):1005-15
references.pmid: 18555844
references.citation: J Ethnopharmacol. 2002 Jul;81(2):199-204
references.pmid: 12065151
references.citation: Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E628-34
references.pmid: 19088257
references.citation: Curr Pharm Des. 2007;13(21):2148-68
references.pmid: 17627547
references.citation: Drugs Today (Barc). 2006 Jan;42(1):39-64
references.pmid: 16511610
references.citation: J Int Med Res. 2008 Jul-Aug;36(4):625-9
references.pmid: 18652756
references.citation: Diabetes Care. 2012 Feb;35(2):342-9
references.pmid: 22190676
references.citation: Endocr J. 2011;58(8):639-46
references.pmid: 21646731
references.citation: J Physiol. 2009 Jul 15;587(Pt 14):3741-50
references.pmid: 19470778
references.citation: Eur J Endocrinol. 2009 Jan;160(1):65-70
references.pmid: 18952766
references.citation: Diabetes. 2008 Jun;57(6):1501-7
references.pmid: 18375437
references.citation: J Clin Invest. 1995 Aug;96(2):741-50
references.pmid: 7635967
references.citation: J Clin Endocrinol Metab. 2000 Jul;85(7):2402-10
references.pmid: 10902785
references.citation: FEBS Lett. 2001 Feb 23;491(1-2):154-8
references.pmid: 11226439
references.citation: Expert Opin Investig Drugs. 2008 Mar;17(3):327-33
references.pmid: 18321232