Fish oil enhances trans-endothelial fatty acids transport and lipid deposition in skeletal muscle by promoting muscular VEGF-B expression via GPR120-CaMKK2-AMPK pathway

Owing to the continuous, tight-junction-sealed architecture of capillary endothelium in skeletal muscle, the trans-endothelial transport of fatty acids from capillary lumen to myofibers constitutes a critical determinant of intramuscular fat (IMF) deposition, thus playing a crucial role in meat quality. This study aimed to investigate the effects of fish oil on trans-endothelial fatty acids transport and lipid deposition in skeletal muscle and explore the underlying vascular regulatory mechanisms. Firstly, preliminary exploratory analyses indicated there may exist an association between IMF content in porcine longissimus dorsi muscle (LDM) and serum VEGF-B level, as well as VEGF-B expression within LDM, hinting at a potential involvement of VEGF-B in skeletal muscle lipid deposition. Meanwhile, the transwell experiments confirmed that VEGF-B enhanced trans-endothelial fatty acid transport by upregulating expression and membrane localization of fatty acid transporters. In addition, DHA, a key bioactive component of fish oil, enhanced trans-endothelial fatty acid transport by promoting VEGF-B expression and secretion of C2C12 myotubes. Mechanistically, the GPR120-CaMKK2-AMPK pathway was involved in DHA-induced VEGF-B expression and secretion. More importantly, fish oil supplementation significantly increased lipid deposition of mice tibialis anterior muscle, alongside the activation of GPR120-CaMKK2-AMPK pathway, the elevated expression of VEGF-B and fatty acid transporters. Overall, these findings suggested that fish oil might enhance trans-endothelial fatty acids transport and lipid deposition in skeletal muscle by promoting muscular VEGF-B expression via GPR120-CaMKK2-AMPK pathway, providing potential molecular targets and nutritional technologies to increase IMF in animal skeletal muscle.