GABPα Promotes Lipid Deposition and Endoplasmic Reticulum Stress by Transcriptional-Regulated ATF4 in Porcine Skeletal Myofibers

Lipid content in myofibers plays an important role in improving pork quality closely linked to flavor, tenderness, and marbling; however, the molecular mechanisms regulating lipid deposition in myofibers remain elusive. Here, we identify GA-binding protein α (GABPα) as a previously unrecognized transcriptional regulator (TF) of lipid deposition in porcine skeletal myofibers. Functional analyses show that GABPα markedly enhances lipid deposition in myofibers and activates endoplasmic reticulum (ER) stress in skeletal muscle. Mechanistically, GABPα directly binds to the promoter of the ER stress-associated gene activating transcription factor 4 (ATF4), thereby promoting lipid deposition in myofibers. Our findings establish GABPα as a novel key regulator of lipid deposition in myofibers and identify the GABPα–ATF4 regulatory axis as a mechanistic pathway connecting ER stress with porcine myofiber lipid deposition, providing significant implications to boost pork quality in the pig industry.