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BMP4 Gene Therapy in Mature Mice Reduces BAT Activation but Protects from Obesity by Browning Subcutaneous Adipose Tissue.

Abstract：

:We examined the effect of Bone Morphogenetic Protein 4 (BMP4) on energy expenditure in adult mature mice by targeting the liver with adeno-associated viral (AAV) BMP4 vectors to increase circulating levels. We verified the direct effect of BMP4 in inducing a brown oxidative phenotype in differentiating preadipocytes in vitro. AAV-BMP4-treated mice display marked browning of subcutaneous adipocytes, with increased mitochondria and Uncoupling Protein 1 (UCP1). These mice are protected from obesity on a high-fat diet and have increased whole-body energy expenditure, improved insulin sensitivity, reduced liver fat, and reduced adipose tissue inflammation. On a control diet, they show unchanged body weight but improved insulin sensitivity. In contrast, AAV-BMP4-treated mice showed beiging of BAT with reduced UCP1, increased lipids, and reduced hormone-sensitive lipase (HSL). Thus, BMP4 exerts different effects on WAT and BAT, but the overall effect is to enhance insulin sensitivity and whole-body energy expenditure by browning subcutaneous adipose tissue.

journal_name

Cell Rep

journal_title

Cell reports

authors

Hoffmann JM,Grünberg JR,Church C,Elias I,Palsdottir V,Jansson JO,Bosch F,Hammarstedt A,Hedjazifar S,Smith U

doi

10.1016/j.celrep.2017.07.020

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

1038-1049

issue

5

issn

2211-1247

pii

S2211-1247(17)30979-8

journal_volume

20

pub_type

杂志文章

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