Oxidative Stress Inhibits Healthy Adipose Expansion Through Suppression of SREBF1-Mediated Lipogenic Pathway.

Abstract:

:Recent studies have emphasized the association of adipose oxidative stress (Fat reactive oxygen species [ROS]) with the pathogenesis of metabolic disorders in obesity. However, the causal roles of Fat ROS in metabolic disturbances in vivo remain unclear because no mouse model has been available in which oxidative stress is manipulated by targeting adipocytes. In this research, we generated two models of Fat ROS-manipulated mice and evaluated the metabolic features in diet-induced obesity. Fat ROS-eliminated mice, in which Cat and Sod1 were overexpressed in adipocytes, exhibited adipose expansion with decreased ectopic lipid accumulation and improved insulin sensitivity. Conversely, Fat ROS-augmented mice, in which glutathione was depleted specifically in adipocytes, exhibited restricted adipose expansion associated with increased ectopic lipid accumulation and deteriorated insulin sensitivity. In the white adipose tissues of these mice, macrophage polarization, tissue fibrosis, and de novo lipogenesis were significantly changed. In vitro approaches identified KDM1A-mediated attenuation of sterol-regulatory element-binding transcription factor 1 (SREBF1) transcriptional activities as the underlying mechanism for the suppression of de novo lipogenesis by oxidative stress. Thus, our study uncovered the novel roles of Fat ROS in healthy adipose expansion, ectopic lipid accumulation, and insulin resistance, providing the possibility for the adipocyte-targeting antioxidant therapy.

journal_name

Diabetes

journal_title

Diabetes

authors

Okuno Y,Fukuhara A,Hashimoto E,Kobayashi H,Kobayashi S,Otsuki M,Shimomura I

doi

10.2337/db17-1032

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1113-1127

issue

6

eissn

0012-1797

issn

1939-327X

pii

db17-1032

journal_volume

67

pub_type

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