Title

MCP-1 Induced Protein Promotes Adipogenesis via Oxidative Stress, Endoplasmic Reticulum Stress and Autophagy

Authors

Authors

C. Younce;P. Kolattukudy

Comments

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Abbreviated Journal Title

Cell. Physiol. Biochem.

Keywords

Monocyte Chemotactic Protein-1; Endoplasmic Reticulum Stress; Oxidative; Stress; Adipogenesis; MCP-1-induced Protein; Autophagy; MONOCYTE CHEMOATTRACTANT PROTEIN-1; ADIPOCYTE DIFFERENTIATION; INSULIN-RESISTANCE; C/EBP-ALPHA; PPAR-GAMMA; ER STRESS; TRANSCRIPTION; PATHWAY; CELLS; MODEL; Cell Biology; Physiology

Abstract

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, endoplasnnic 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. Inhibition of autophagy by specific inhibitors or knockdown of beclin-1 attenuated adipogenesis. These results demonstrate that MCPIP mediates adipogenesis via ROS/RNS production that causes ER stress that leads to autophagy required for adipocyte differentiation, that plays an important role in obesity. Copyright (C) 2012 S. Karger AG, Basel

Journal Title

Cellular Physiology and Biochemistry

Volume

30

Issue/Number

2

Publication Date

1-1-2012

Document Type

Article

Language

English

First Page

307

Last Page

320

WOS Identifier

WOS:000306682000002

ISSN

1015-8987

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