AMPK Mediates Early Activation of the Unfolded Protein Response through a Positive Feedback Loop in Palmitate-Treated Muscle Cells

Background: Activation of the unfolded protein response (UPR) is closely related to pathogenesis many metabolic disorders. Accumulating evidence also shows that UPR and signaling pathways are interdependent. The AMP-activated kinase (AMPK) signal pathway controls energy balance eukaryotes. aim this study was therefore investigate possible interaction between AMPK in muscle cells exposed saturated fatty acids, as well potential mechanism. Methods: acid palmitate used induce C2C12 myotubes. Compound C or knockdown AMPKα with short hairpin RNA (shRNA) were inhibit palmitate-treated cells. myotubes activated using 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICAR) ex229. pre-treated taurourdodeoxycholic (TUDCA) before adding palmitate. Real-time PCR Western blotting performed evaluate expression markers activation AMPK. Results: Palmitate treatment induced while activating signaling. Inhibition compound shRNA reduced palmitate-induced UPR, inhibition TUDCA activation. This indicates a positive feedback loop Furthermore, AICAR ex229 caused dose-dependent upregulation markers, including transcription factor 4 (ATF4), binding immunoglobulin (BIP), growth arrest DNA damage-inducible 34 (GADD34) protein. Conclusions: These results provide first involved early by acids skeletal muscle. they indicate physiological pharmacological (e.g., exercise phenformin, respectively) can promote health function, thereby improving quality life individuals disorders due high-fat diet obesity.