Related Experiment Video
Updated: Oct 15, 2025
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Free Fatty Acid Impairs Myogenic Differentiation through the AMPKα-MicroRNA 206 Pathway
Aiwen Jiang1, Hongyun Guo1, Liangliang Zhang1
1Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural Universitygrid.27871.3b, Nanjing, China.
Abstract:
The activity of AMP-activated protein kinase α (AMPKα) is reduced in type 2 diabetes, and type 2 diabetes is associated with muscular atrophy. To date, there is little known about the mechanism by which free fatty acid (FFA) participates in muscular impairment. The purpose of the present study was to explore whether FFA damages myogenesis through the AMPKα-histone deacetylase 4 (HDAC4)-microRNA 206 (miR-206) pathway. The results showed that 1 mM FFA produced lipid accumulation, significantly impaired the insulin signaling pathway, and decreased the myogenic differentiation of C2C12 myoblast cells. FFA reduced the LKB1-AMPKα pathway, and the activation of AMPKα rescued the myogenic impairment caused by FFA (P < 0.05). AMPKα promoted myogenesis by regulating the expression of miR-206 through HDAC4 (P < 0.05) and affected the cell cycle and cell proliferation to promote myogenesis by regulating miR-206 and miR-206's target cyclin D1 gene. In addition, AICAR (5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside) and HDAC4 small interfering RNA (siRNA) promoted myogenic differentiation compared with the FFA group; however, this positive effect was significantly downregulated after transfection with the miR-206 inhibitor. In summary, AMPKα plays positive roles in myogenic differentiation and myogenesis, and FFA decreased myogenic differentiation and myotube formation through the AMPKα-HDAC4-miR-206 pathway.
Insights
Free fatty acids impair muscle cell development by disrupting the AMPKα-HDAC4-miR-206 pathway. Activating AMP-activated protein kinase α (AMPKα) can reverse this damage, promoting muscle growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Type 2 diabetes is linked to reduced AMP-activated protein kinase α (AMPKα) activity and muscle atrophy.
- The role of free fatty acids (FFAs) in muscle impairment is not fully understood.
Purpose of the Study:
- To investigate if FFAs induce muscle cell damage via the AMPKα-histone deacetylase 4 (HDAC4)-microRNA 206 (miR-206) pathway.
- To explore the mechanisms underlying FFA-induced muscle impairment.
Main Methods:
- Utilized C2C12 myoblast cells treated with FFA.
- Assessed insulin signaling, myogenic differentiation, and the AMPKα pathway.
- Investigated the roles of AMPKα, HDAC4, and miR-206 using activators, inhibitors, and small interfering RNA (siRNA).
Main Results:
- FFA treatment led to lipid accumulation, impaired insulin signaling, and reduced myogenic differentiation in C2C12 cells.
- FFA decreased LKB1-AMPKα pathway activity; AMPKα activation rescued FFA-induced myogenic impairment.
- AMPKα regulated miR-206 expression via HDAC4, promoting myogenesis by affecting cell cycle and proliferation through miR-206 and its target, cyclin D1.
Conclusions:
- AMPKα activation positively influences myogenic differentiation and myogenesis.
- FFAs impair myogenic differentiation and myotube formation by downregulating the AMPKα-HDAC4-miR-206 pathway.
More Related Videos
Related Concept Videos
01:13Formation of Muscle Fibers from Myoblasts
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
01:25cAMP-dependent Protein Kinase Pathways