MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy.
Obesity involves inflammation. MCP-1, an inflammatory chemokine, and MCP-1-induced protein (MCPIP) are known to induce adipogenesis that causes increase in the number of adipocytes. Here we elucidate the intermediate processes through which MCPIP induces adipogenesis. Forced expression of MCPIP in 3T3-L1 preadipocytes caused increased reactive oxygen/nitrogen species (ROS/RNS) production and inducible-nitric oxide synthase (iNOS) expression, endoplasmic reticulum stress (ER), as indicated by expression of ER chaperones and protein disulfide isomerase, and autophagy as indicated by expression of beclin-1 and cleavage of LC3. Treatment of ROS inhibitor, apocynin attenuated MCPIP induction of adipogenesis as measured by the induction of transcription factors involved in adipogenesis, adipocyte markers and lipid droplet accumulation. Inhibition of ER stress with taurursodeoxycholate or knockdown of inositol requiring enzyme 1 (IRE1) inhibited MCPIP induced autophagy and adipogenesis. Preadipocytes in adipogenesis-inducing cocktail manifested ER stress and autophagy. Knockdown of MCPIP attenuated these effects. MCPIP induced p38 activation and p38 inhibitor, SB203580, attenuated MCPIP-induced adipogenesis.
Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826, USA.
Craig
C
Younce
Pappachan
P
Kolattukudy
D041721:3T3-L1 Cells; D000098:Acetophenones / Q000494:pharmacology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012260:Ribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000098:Acetophenones; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007093:Imidazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C056165:acetovanillone; D052247:Nitric Oxide Synthase Type II; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004722:Endoribonucleases; D012260:Ribonucleases; C541320:Zc3h12a protein, mouse; C093642:SB 203580