The myokine meteorin‐like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2. (19th April 2020)

• Record Type: Journal Article
• Authors: Lee, Jung Ok; Byun, Won Seok; Kang, Min Ju; Han, Jeong Ah; Moon, Jiyoung; Shin, Min‐Jeong; Lee, Ho Jun; Chung, Ji Hyung; Lee, Jin‐Seok; Son, Chang‐Gue; Song, Kwon‐Ho; Kim, Tae Woo; Lee, Eun‐Soo; Kim, Hong Min; Chung, Choon Hee; Ngoei, Kevin R. W.; Ling, Naomi X. Y.; Oakhill, Jonathan S.; Galic, Sandra; Murray‐Segal, Lisa; Kemp, Bruce E.; Kim, Kyoung Min; Lim, Soo; Kim, Hyeon Soo
• Is Part Of: FEBS journal. Volume 287:Number 10(2020)
• Page Start: 2087
• Page End: 2104
• Publication Date: 2020-04-19
• Subjects: adipomyokine -- AMPK -- glucose uptake -- Metrnl -- type 2 diabetes; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15301
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Meteorin‐like (metrnl) is a recently identified adipomyokine that beneficially affects glucose metabolism; however, its underlying mechanism of action is not completely understood. We here show that the level of metrnl increases in vitro under electrical pulse stimulation and in vivo in exercised mice, suggesting that metrnl is secreted during muscle contractions. In addition, metrnl increases glucose uptake via the calcium‐dependent AMPKα2 pathway in skeletal muscle cells and increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPKα2‐dependent manner. Phosphorylated HDAC5 interacts with 14‐3‐3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. An intraperitoneal injection of recombinant metrnl improved glucose tolerance in mice with high‐fat‐diet‐induced obesity or type 2 diabetes, but not in AMPK β1β2 muscle‐specific null mice. Metrnl improves glucose metabolism via AMPKα2 and is a promising therapeutic candidate for glucose‐related diseases such as type 2 diabetes. Abstract : We found that metrnl, known as an adipomyokine, is secreted during muscle contractions. Metrnl increases glucose uptake via AMPKα in skeletal muscle cells and increases the phosphorylation of HDAC5 and TBC1D1 in AMPKα‐dependent manner. Recombinant metrnl improves glucose tolerance in mice with obesity or type 2 diabetes. These results suggest that metrnl is a promising therapeutic candidate for diabetes.