A family of Acrp30/adiponectin structural and functional paralogs.
Biochemical, genetic, and animal studies in recent years have established a critical role for the adipokine Acrp30/adiponectin in controlling whole-body metabolism, particularly by enhancing insulin sensitivity in muscle and liver, and by increasing fatty acid oxidation in muscle. We describe a widely expressed and highly conserved family of adiponectin paralogs designated as C1q/tumor necrosis factor-alpha-related proteins (CTRPs) 1-7. In the present study, we focus on mCTRP2, the mouse paralog most similar to adiponectin. At nanomolar concentrations, bacterially produced mCTRP2 rapidly induced phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, and mitogen-activated protein kinase in C2C12 myotubes, which resulted in increased glycogen accumulation and fatty acid oxidation. The discovery of a family of adiponectin paralogs has implications for understanding the control of energy homeostasis and could provide new targets for pharmacologic intervention in metabolic diseases such as diabetes and obesity.
Wong
Guang W
GW
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Wang
Jin
J
Hug
Christopher
C
Tsao
Tsu-Shuen
TS
Lodish
Harvey F
HF
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D052242:Adiponectin; D000818:Animals; D019556:COS Cells; D005227:Fatty Acids / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D052242:Adiponectin; D005227:Fatty Acids; D036341:Intercellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D011994:Recombinant Proteins; D006003:Glycogen; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase