The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2.

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.

• Authors: Jung Ok Lee, Won Seok Byun, Min Ju Kang, Jeong Ah Han, Jiyoung Moon, Min-Jeong Shin, Ho Jun Lee, Ji Hyung Chung, Jin-Seok Lee, Chang-Gue Son, Kwon-Ho Song, Tae Woo Kim, Eun-Soo Lee, Hong Min Kim, Choon Hee Chung, Kevin R W Ngoei, Naomi X Y Ling, Jonathan S Oakhill, Sandra Galic, Lisa Murray-Segal, Bruce E Kemp, Kyoung Min Kim, Soo Lim, Hyeon Soo Kim
• Journal: The FEBS journal (FEBS J) Vol. 287 Issue 10 Pg. 2087-2104 (05 2020) ISSN: 1742-4658 [Electronic] England
• PMID: 32196931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Chemical References

• 14-3-3 Proteins
• Glucose Transporter Type 4
• Nerve Growth Factors
• Recombinant Proteins
• Slc2a4 protein, mouse
• cometin protein, mouse
• AMPK alpha2 subunit, mouse
• AMP-Activated Protein Kinases
• Hdac5 protein, mouse
• Histone Deacetylases
• Glucose

Topics

• 14-3-3 Proteins (genetics)
• AMP-Activated Protein Kinases (genetics)
• Animals
• Cell Line
• Diabetes Mellitus, Type 2 (drug therapy, genetics, pathology)
• Diet, High-Fat (adverse effects)
• Electric Stimulation
• Glucose (genetics, metabolism)
• Glucose Transporter Type 4 (genetics)
• Histone Deacetylases (genetics)
• Humans
• Insulin Resistance (genetics)
• Mice
• Muscle Contraction (genetics)
• Muscle, Skeletal (metabolism, pathology)
• Nerve Growth Factors (genetics, pharmacology)
• Obesity (drug therapy, etiology, genetics, pathology)
• Physical Conditioning, Animal
• Recombinant Proteins (pharmacology)