title: Autophagy regulates inflammation in adipocytes.
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.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan. yosizaki@belle.shiga-med.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Chisato
authors.initials: C
authors.lastname: Kusunoki
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kondo
authors.forename: Mako
authors.initials: M
authors.lastname: Yasuda
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.forename: Katsutaro
authors.initials: K
authors.lastname: Morino
authors.forename: Osamu
authors.initials: O
authors.lastname: Sekine
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ugi
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nishio
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
mesh_terms: D041721:3T3-L1 Cells; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017667:Adipocytes / Q000473:pathology*; D000818:Animals; D001343:Autophagy; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D007333:Insulin Resistance; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; C025946:3-methyladenine; D000225:Adenine