GDF15 mediates the metabolic effects of PPARβ/δ by activating AMPK

被引：69

作者：

Aguilar-Recarte, David ^{[1
,2
,3
,4
]}

Barroso, Emma ^{[1
,2
,3
,4
]}

Guma, Anna ^{[2
,3
,5
]}

Pizarro-Delgado, Javier ^{[1
,2
,3
,4
]}

Pena, Lucia ^{[1
,2
,3
,4
]}

Ruart, Maria ^{[1
,2
,3
,4
]}

Palomer, Xavier ^{[1
,2
,3
,4
]}

Wahli, Walter ^{[6
,7
,8
]}

Vazquez-Carrera, Manuel ^{[1
,2
,3
,4
]}

机构：

[1] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharmacol Toxicol & Therapeut Chem, Barcelona 08028, Spain

[2] Univ Barcelona, Inst Biomed Univ Barcelona IBUB, Barcelona 08028, Spain

[3] Inst Salud Carlos III, Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain

[4] Hosp St Joan de Deu, Pediat Res Inst, Esplugas de Llobregat 08950, Spain

[5] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biomed, Barcelona 08028, Spain

[6] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland

[7] Nanyang Technol Univ Singapore, Lee Kong Chian Sch Med, Singapore 308232, Singapore

[8] INRAE, UMR1331, ToxAlim Res Ctr Food Toxicol, F-31300 Toulouse, France

来源：

CELL REPORTS | 2021年 / 36卷 / 06期

关键词：

ENDOPLASMIC-RETICULUM STRESS; BETA SUPERFAMILY MEMBER; GROWTH-FACTOR-BETA; INSULIN-RESISTANCE; SKELETAL-MUSCLE; WEIGHT-LOSS; RECEPTOR; P53; EXPRESSION; MICE;

D O I：

10.1016/j.celrep.2021.109501

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examine whether PPAR beta/delta activation effects depend on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPAR beta/delta activation increases GDF15 levels and ameliorates glucose intolerance, fatty acid oxidation, endoplasmic reticulum stress, and inflammation, and activates AMPK in HFD-fed mice, whereas these effects are abrogated by the injection of a GDF15 neutralizing antibody and in Gdf15(-/-) mice. The AMPK-p53 pathway is involved in the PPAR beta/delta-mediated increase in GDF15, which in turn activates again AMPK. Consistently, Gdf15(-/-) mice show reduced AMPK activation in skeletal muscle, whereas GDF15 administration results in AMPK activation in this organ. Collectively, these data reveal a mechanism by which PPAR beta/delta activation increases GDF15 levels via AMPK and p53, which in turn mediates the metabolic effects of PPAR beta/delta by sustaining AMPK activation.

引用

页数：20

共 58 条

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