SBP2 deficiency in adipose tissue macrophages drives insulin resistance in obesity.

Abstract:

:Proinflammatory activation and accumulation of adipose tissue macrophages (ATMs) are associated with increased risk of insulin resistance in obesity. Here, we described the previously unidentified role of selenocysteine insertion sequence-binding protein 2 (SBP2) in maintaining insulin sensitivity in obesity. SBP2 was suppressed in ATMs of diet-induced obese mice and was correlated with adipose tissue inflammation. Loss of SBP2 initiated metabolic activation of ATMs, inducing intracellular reactive oxygen species content and inflammasome, which subsequently promoted IL-1β-associated local proliferation and infiltration of proinflammatory macrophages. ATM-specific knockdown of SBP2 in obese mice promoted insulin resistance by increasing fat tissue inflammation and expansion. Reexpression of SBP2 improved insulin sensitivity. Last, an herbal formula that specifically induced SBP2 expression in ATMs can experimentally improve insulin sensitivity. Clinical observation revealed that it improved hyperglycemia in patients with diabetes. This study identified SBP2 in ATMs as a potential target in rescuing insulin resistance in obesity.

journal_name

Sci Adv

journal_title

Science advances

authors

Wang N,Tan HY,Li S,Wang D,Xu Y,Zhang C,Xia W,Che CM,Feng Y

doi

10.1126/sciadv.aav0198

subject

Has Abstract

pub_date

2019-08-14 00:00:00

pages

eaav0198

issue

8

issn

2375-2548

pii

aav0198

journal_volume

5

pub_type

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