title: Naringenin inhibits adipogenesis and reduces insulin sensitivity and adiponectin expression in adipocytes.
abstract: Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells.
authors: Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors: Allison J
authors: AJ
authors: Richard
authors: Zhaleh
authors: Z
authors: Amini-Vaughan
authors: David M
authors: DM
authors: Ribnicky
authors: Jacqueline M
authors: JM
authors: Stephens
references: Br J Nutr. 2013 Mar 28;109(6):1040-51
references: 22850125
references: J Nutr. 2001 Feb;131(2):235-41
references: 11160539
references: J Biol Chem. 2003 Dec 5;278(49):49530-6
references: 14522993
references: Mol Cell Biol. 1994 Jul;14(7):4902-11
references: 8007986
references: Diabetes Obes Metab. 2008 Nov;10(11):1097-104
references: 18355329
references: Eur J Clin Nutr. 2007 Apr;61(4):472-7
references: 17047689
references: J Biol Chem. 1991 Nov 15;266(32):21839-45
references: 1939208
references: Am J Physiol Gastrointest Liver Physiol. 2000 Dec;279(6):G1148-54
references: 11093936
references: Nature. 2001 Feb 8;409(6821):729-33
references: 11217863
references: Proc Natl Acad Sci U S A. 1982 Feb;79(3):845-9
references: 6174983
references: Phytother Res. 2009 Jul;23(7):948-54
references: 19153985
references: Nat Genet. 2000 Sep;26(1):13
references: 10973236
references: J Clin Invest. 2007 Sep;117(9):2621-37
references: 17717599
references: Am J Physiol Cell Physiol. 2001 Apr;280(4):C807-13
references: 11245597
references: Expert Rev Cardiovasc Ther. 2012 Jul;10(7):933-9
references: 22908926
references: Am J Prev Med. 2012 Jun;42(6):563-70
references: 22608371
references: Biochem Biophys Res Commun. 1995 Apr 6;209(1):343-8
references: 7726855
references: Proc Natl Acad Sci U S A. 1978 Dec;75(12):6107-9
references: 282628
references: J Biol Chem. 1996 Oct 11;271(41):25227-32
references: 8810283
references: Eur J Nutr. 2010 Mar;49(2):101-9
references: 19727895
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: Mol Endocrinol. 1997 Sep;11(10):1552-62
references: 9280070
references: Annu Rev Biochem. 1995;64:345-73
references: 7574486
references: Nig Q J Hosp Med. 2008 Jan-Mar;18(1):16-20
references: 19062465
references: Nutrition. 2008 Oct;24(10):1039-44
references: 18595661
references: Diabetes. 2003 Oct;52(10):2554-61
references: 14514640
references: Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1766-70
references: 22815342
references: J Altern Complement Med. 2005 Apr;11(2):369-71
references: 15865506
references: Am J Physiol. 1994 Feb;266(2 Pt 1):C319-34
references: 8141246
references: Mol Cell Endocrinol. 2010 Jul 29;323(2):208-14
references: 20363289
references: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):44-9
references: 12502791
references: Biochem Biophys Res Commun. 2010 Jul 23;398(2):178-83
references: 20558145
references: Diabetes. 2009 Oct;58(10):2198-210
references: 19592617
references: J Biol Chem. 1994 Jan 7;269(1):1-4
references: 8276779
references: Biochem Biophys Res Commun. 2003 May 30;305(2):229-34
references: 12745063
references: Annu Rev Med. 1998;49:235-61
references: 9509261
references: Evid Based Complement Alternat Med. 2013;2013:627375
references: 23634172
references: Mol Nutr Food Res. 2011 May;55 Suppl 1:S26-34
references: 21280205
references: J Lipid Res. 2013 Mar;54(3):711-724
references: 23269394
references: Mol Cell Biol. 2009 Mar;29(6):1575-91
references: 19114551
references: Phytother Res. 2008 Oct;22(10):1400-3
references: 18690615
references: Nat Methods. 2012 Jul;9(7):671-5
references: 22930834
references: Am J Clin Nutr. 2010 Jan;91(1):258S-261S
references: 19906806
references: Biochem Biophys Res Commun. 1999 Nov 19;265(2):410-5
references: 10558881
references: Am J Physiol Endocrinol Metab. 2002 Sep;283(3):E413-22
references: 12169433