Genetic Liver-Specific AMPK Activation Protects against Diet-Induced Obesity and NAFLD

被引：241

作者：

Garcia, Daniel ^{[1
]}

Hellberg, Kristina ^{[1
]}

Chaix, Amandine ^{[2
]}

Wallace, Martina ^{[5
]}

Herzig, Sebastien ^{[1
]}

Badur, Mehmet G. ^{[5
]}

Lin, Terry ^{[2
]}

Shokhirev, Maxim N. ^{[3
]}

Pinto, Antonio F. M. ^{[4
]}

Ross, Debbie S. ^{[1
]}

Saghatelian, Alan ^{[4
]}

Panda, Satchidananda ^{[2
]}

Dow, Lukas E. ^{[6
]}

Metallo, Christian M. ^{[5
]}

Shaw, Reuben J. ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA

[2] Salk Inst Biol Studies, Regulatory Biol Lab, La Jolla, CA 92037 USA

[3] Salk Inst Biol Studies, Razavi Newman Integrat Genom & Bioinformat Core, La Jolla, CA 92037 USA

[4] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA

[5] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[6] Weill Cornell Med, Dept Med, Sandra & Edward Meyer Canc Ctr, New York, NY 10021 USA

来源：

CELL REPORTS | 2019年 / 26卷 / 01期

关键词：

HEPATIC STEATOSIS; PHOSPHORYLATION; HOMEOSTASIS; MECHANISMS; KINASE; SUBUNIT; TARGET; WATER; MICE;

D O I：

10.1016/j.celrep.2018.12.036

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The AMP-activated protein kinase (AMPK) is a highly conserved master regulator of metabolism, whose activation has been proposed to be therapeutically beneficial for the treatment of several metabolic diseases, including nonalcoholic fatty liver disease (NAFLD). NAFLD, characterized by excessive accumulation of hepatic lipids, is the most common chronic liver disease and a major risk factor for development of nonalcoholic steatohepatitis, type 2 diabetes, and other metabolic conditions. To assess the therapeutic potential of AMPK activation, we have generated a genetically engineered mouse model, termed iAMPK(CA), where AMPK can be inducibly activated in vivo in mice in a spatially and temporally restricted manner. Using this model, we show that liver-specific AMPK activation reprograms lipid metabolism, reduces liver steatosis, decreases expression of inflammation and fibrosis genes, and leads to significant therapeutic benefits in the context of diet-induced obesity. These findings further support AMPK as a target for the prevention and treatment of NAFLD.

引用

页码：192 / +

页数：23

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