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Role of Angptl4/Fiaf in exercise-induced skeletal muscle AMPK activation.
- Source :
-
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2018 Sep 01; Vol. 125 (3), pp. 715-722. Date of Electronic Publication: 2018 Jun 28. - Publication Year :
- 2018
-
Abstract
- Angiopoietin-like protein 4 (Angptl4)/fasting-induced adipose factor (Fiaf) expression levels are increased by exercise in skeletal muscle. We have previously shown that Angptl4 regulates food intake and energy expenditure via modulation of hypothalamic AMP-activated protein kinase (AMPK) activity. AMPK is an important signaling molecule that integrates skeletal muscle metabolism during exercise. Therefore, we investigated the involvement of Angptl4 in exercise-induced AMPK activation in skeletal muscle. Angptl4 protein and mRNA expression levels were significantly increased in the gastrocnemius and soleus muscles of mice following a 50-min running bout. Treatment of C2C12 myotubes with Angptl4 increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), which were markers of AMPK activation, and the mitochondrial maximum respiratory capacity. Treadmill exercise increased AMPK and ACC phosphorylation in the gastrocnemius of normal mice; this phosphorylation increase was attenuated in mice lacking Angptl4. Endurance to swimming and hanging was also reduced in Angptl4 knockout mice. Taken together, our current data demonstrate that exercise-induced upregulation of skeletal muscle Angptl4 is critical for AMPK activation and exercise tolerance. These findings unveil a new role for skeletal muscle Angptl4 in exercise physiology. NEW & NOTEWORTHY 1) Angiopoietin-like protein 4 (Angptl4) treatment activates AMP-activated protein kinase (AMPK) signaling in skeletal muscle cells. 2) Angptl4 increases the maximum mitochondrial oxidative capacity through AMPK activation in skeletal muscle cells. 3) Lack of Angptl4 mitigates exercise-induced skeletal muscle AMPK activation. 4) Angptl4-deficient mice show a lower endurance to exercise.
- Subjects :
- AMP-Activated Protein Kinases metabolism
Acetyl-CoA Carboxylase metabolism
Angiopoietin-Like Protein 4 metabolism
Animals
Enzyme Activation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria, Muscle enzymology
Mitochondria, Muscle metabolism
Muscle Fibers, Skeletal metabolism
Physical Endurance physiology
RNA, Messenger biosynthesis
RNA, Messenger genetics
Swimming physiology
AMP-Activated Protein Kinases physiology
Angiopoietin-Like Protein 4 genetics
Muscle, Skeletal enzymology
Muscle, Skeletal physiology
Physical Exertion physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1601
- Volume :
- 125
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of applied physiology (Bethesda, Md. : 1985)
- Publication Type :
- Academic Journal
- Accession number :
- 29952246
- Full Text :
- https://doi.org/10.1152/japplphysiol.00984.2016