Details

Autor(en) / Beteiligte

• Kumagai, Hiroshi
• Coelho, Ana Raquel
• Wan, Junxiang
• Huang, Amy
• Mehta, Hemal H
• Yen, Kelvin
• Zempo, Hirofumi
• Fuku, Noriyuki
• Oliveira, Paulo J
• Cohen, Pinchas
• Kim, Su-Jeong

Titel

MOTS‐c inhibits high‐fat diet‐induced muscle wasting by suppressing myostatin expression via the PTEN/AKT/FOXO1 signaling pathway

Ist Teil von

• The FASEB journal, 2020-04, Vol.34 (S1), p.1-1

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Abstract only Insulin resistance is thought to contribute to the development of muscle wasting. MOTS‐c, a novel mitochondrial‐derived peptide, improves insulin resistance in skeletal muscle, but its effects on muscle wasting have yet to be explored. Here, we used a diet‐induced obese mouse model to examine the effect of MOTS‐c administration on high fat diet‐induced muscle wasting. Three weeks of MOTS‐c administration by intraperitoneal (IP) injection in high‐fat diet fed mice resulted in higher total skeletal muscle mass of soleus, gastrocnemius, and plantaris compared to its high‐fat diet fed control group. Myostatin mRNA expression levels were significantly decreased in the MOTS‐c treated group compared to the high‐fat diet fed controls in the gastrocnemius muscle. Furthermore, myostatin mRNA expression negatively correlated with the total skeletal muscle mass of soleus, gastrocnemius, and plantaris. To examine the detailed mechanism of MOTS‐c action, we injected high‐fat diet fed mice with MOTS‐c for eight weeks and detected significantly lower plasma myostatin levels than high‐fat diet fed controls, as well as mRNA expression of myostatin and atrogin‐1 in the skeletal muscle. We further examined the upstream signaling pathways of myostatin regulation in the skeletal muscle and showed that MOTS‐c treatment inhibited PTEN activity, leading to elevated AKT phosphorylation and inhibition of FOXO1 transcription activity, resulting in myostatin and atrogin‐1 suppression. These results suggest that potent MOTS‐c analogues could potentially treat conditions such as high‐fat diet‐induced skeletal muscle wasting, as well as other muscle wasting phenotypes including sarcopenia, and that circulating levels of myostatin may serve as a pharmacodynamic biomarker of MOTS‐c activity.