title: Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes.
abstract: Telomere shortening is emerging as a biological indicator of accelerated aging and aging-related diseases including type 2 diabetes. While telomere length measurements were largely done in white blood cells, there is lack of studies on telomere length in relation to oxidative stress in target tissues affected in diabetes. Therefore, the aim of this study is to induct oxidative stress in adipocytes and to test whether these adipocytes exhibit shortened telomeres, senescence and functional impairment. 3T3-L1 adipocytes were subjected to oxidative stress and senescence induction by a variety of means for 2 weeks (exogenous application of H2O2, glucose oxidase, asymmetric dimethylarginine (ADMA) and glucose oscillations). Cells were probed for reactive oxygen species generation (ROS), DNA damage, mRNA and protein expression of senescent and pro-inflammatory markers, telomere length and glucose uptake. Compared to untreated cells, both ROS generation and DNA damage were significantly higher in cells subjected to oxidative stress and senescence. Adipocytes subjected to oxidative stress also showed shortened telomeres and increased mRNA and protein expression of p53, p21, TNF alpha and IL-6. Senescent cells were also characterized by decreased levels of adiponectin and impaired glucose uptake. Briefly, adipocytes under oxidative stress exhibited increased ROS generation, DNA damage, shortened telomeres and switched to senescent/pro-inflammatory phenotype with impaired glucose uptake.
authors: Madras Diabetes Research Foundation, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre of Education, Gopalapuram, Chennai 600 086, India.
authors: Finny
authors: F
authors: Monickaraj
authors: Sankaramoorthy
authors: S
authors: Aravind
authors: Pichamoorthy
authors: P
authors: Nandhini
authors: Paramasivam
authors: P
authors: Prabu
authors: Chandrakumar
authors: C
authors: Sathishkumar
authors: Viswanathan
authors: V
authors: Mohan
authors: Muthuswamy
authors: M
authors: Balasubramanyam
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005949:Glucose Oxidase / Q000378:metabolism* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species; D016615:Telomere / Q000737:chemistry / Q000187:drug effects*; D059506:Telomere Shortening / Q000187:drug effects* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D015415:Biomarkers; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C018524:N,N-dimethylarginine; D001120:Arginine; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D054462:p21-Activated Kinases; D005947:Glucose
references: Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):692-7
references: 18239148
references: Cell Physiol Biochem. 2009;24(1-2):115-24
references: 19590199
references: Cell. 2005 Feb 25;120(4):513-22
references: 15734683
references: Int J Biochem Cell Biol. 2006;38(5-6):794-803
references: 16442834
references: Cell Metab. 2010 May 5;11(5):379-89
references: 20444418
references: J Endocrinol. 2012 Apr;213(1):67-76
references: 22281526
references: J Biol Chem. 2006 Sep 8;281(36):26602-14
references: 16809344
references: Diabetes Res Clin Pract. 2011 Feb;91(2):171-6
references: 21146886
references: J Clin Invest. 2003 Dec;112(12):1796-808
references: 14679176
references: Circ Res. 2007 Jan 5;100(1):15-26
references: 17204661
references: Cell Metab. 2012 Jan 4;15(1):51-64
references: 22225876
references: Mol Cell. 2004 May 21;14(4):501-13
references: 15149599
references: J Atheroscler Thromb. 2011;18(7):545-50
references: 21551960
references: Aging Cell. 2010 Oct;9(5):667-84
references: 20701600
references: Indian J Med Res. 2007 Mar;125(3):441-50
references: 17496367
references: Vasc Med. 2005 Jul;10 Suppl 1:S65-71
references: 16444871
references: Nat Med. 2009 Sep;15(9):996-7
references: 19734871
references: Clin Geriatr Med. 2008 Aug;24(3):395-405, v
references: 18672179
references: Nucleic Acids Res. 2002 May 15;30(10):e47
references: 12000852
references: PLoS One. 2011 Jan 20;6(1):e15813
references: 21283750
references: Diabetes Care. 2006 Feb;29(2):283-9
references: 16443874
references: Chem Pharm Bull (Tokyo). 2011;59(7):839-43
references: 21720033
references: Mol Cell Biochem. 2012 Jun;365(1-2):343-50
references: 22411737
references: Diabetologia. 2011 May;54(5):1219-26
references: 21287141
references: Cell Cycle. 2007 Jun 1;6(11):1284-7
references: 17534147
references: Science. 1993 Jan 1;259(5091):87-91
references: 7678183
references: Diabetes. 2010 Nov;59(11):2949-59
references: 20802255
references: Exp Cell Res. 2008 Jun 10;314(9):1918-22
references: 18282568
references: Exp Gerontol. 2011 Jul;46(7):517-23
references: 21397002
references: J Ren Nutr. 2012 Jan;22(1):86-9
references: 22200421
references: Nat Med. 2009 Sep;15(9):1082-7
references: 19718037
references: Exp Cell Res. 1988 Mar;175(1):184-91
references: 3345800
references: Int J Biochem Cell Biol. 2007;39(9):1673-84
references: 17540609
references: J Pediatr Endocrinol Metab. 2011;24(11-12):953-7
references: 22308847
references: Atherosclerosis. 2010 Mar;209(1):42-50
references: 19889414
references: Mol Cell Biochem. 2011 May;351(1-2):197-205
references: 21249428
references: Diabet Med. 2005 Sep;22(9):1151-6
references: 16108841
references: Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E210-8
references: 17389708