RRC ID 12692
Author Yoshizaki T, Kusunoki C, Kondo M, Yasuda M, Kume S, Morino K, Sekine O, Ugi S, Uzu T, Nishio Y, Kashiwagi A, Maegawa H.
Title Autophagy regulates inflammation in adipocytes.
Journal Biochem. Biophys. Res. Commun.
Abstract Autophagy is an essential process for both the maintenance and the survival of cells, with homeostatic low levels of autophagy being critical for intracellular organelles and proteins. In insulin resistant adipocytes, various dysfunctional/damaged molecules, organelles, proteins, and end-products accumulate. However, the role of autophagy (in particular, whether autophagy is activated or not) is poorly understood. In this study we found that in adipose tissue of insulin resistant mice and hypertrophic 3T3-L1 adipocytes autophagy was suppressed. Also in hypertrophic adipocytes, autophagy-related gene expression, such as LAMP1, LAMP2, and Atg5 was reduced, whereas gene expression in the inflammatory-related genes, such as MCP-1, IL-6, and IL-1β was increased. To find out whether suppressed autophagy was linked to inflammation we used the autophagy inhibitor, 3-methyladenine, to inhibit autophagy. Our results suggest that such inhibition leads to an increase in inflammatory gene expression and causes endoplasmic reticulum (ER) stress (which can be attenuated by treatment with the ER stress inhibitor, Tauroursodeoxycholic Acid). Conversely, the levels of inflammatory gene expression were reduced by the activation of autophagy or by the inhibition of ER stress. The results indicate that the suppression of autophagy increases inflammatory responses via ER stress, and also defines a novel role of autophagy as an important regulator of adipocyte inflammation in systemic insulin resistance.
Volume 417(1)
Pages 352-7
Published 2012-1-6
DOI 10.1016/j.bbrc.2011.11.114
PII S0006-291X(11)02135-8
PMID 22155234
MeSH 3T3-L1 Cells Adenine / analogs & derivatives Adenine / pharmacology Adipocytes / pathology* Animals Autophagy* Endoplasmic Reticulum Stress* Gene Expression Regulation Green Fluorescent Proteins / genetics Inflammation / genetics Inflammation / pathology* Insulin Resistance Mice Mice, Transgenic Microtubule-Associated Proteins / genetics
IF 2.705
Times Cited 42
Mice GFP-LC3#53 (RBRC00806)