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White-to-brown metabolic conversion of human adipocytes by JAK inhibition.

Abstract：

:The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of new therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus kinase (JAK) activity with no precedent in adipose tissue biology that stably confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a previously unknown role for the JAK-STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Moisan A,Lee YK,Zhang JD,Hudak CS,Meyer CA,Prummer M,Zoffmann S,Truong HH,Ebeling M,Kiialainen A,Gérard R,Xia F,Schinzel RT,Amrein KE,Cowan CA

doi

10.1038/ncb3075

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

57-67

issue

1

eissn

1465-7392

issn

1476-4679

pii

ncb3075

journal_volume

17

pub_type

杂志文章

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