Dietary phospholipids alleviate high fat diet-induced intestinal lipid deposition through ATF4-PPARα-MTTP/SAR1B pathway in yellow catfish

Phospholipids serve as an efficient emulsifier and transport carrier for lipids. However, the regulatory mechanism by which phospholipids ameliorate lipid metabolic disorders induced by high-fat diet (HFD) remains unclear. The study aimed to investigate the effects and regulatory mechanisms of dietary phospholipids and HFD on intestinal lipid metabolism. We found that dietary phospholipids alleviated HFD-induced intestinal lipid deposition by inhibiting sterol regulatory element binding proteins 1 (SREBP1)-dependent lipogenesis and promoting peroxisome proliferator-activated receptor α (PPARα)-dependent lipolysis. Dietary phospholipids alleviated HFD-induced impairment in chylomicrons (CMs) synthesis and secretion by promoting microsomal triglyceride transfer protein (MTTP), apolipoprotein B and secretion-associated, Ras-related GTPase 1b (SAR1B) mRNA and protein expression. Moreover, dietary phospholipids alleviated the reduction in phosphatidylcholine synthesis induced by HFD via promoting cytidine triphosphate: phosphocholine cytidylyltransferase (CCTα) protein expression and mitigated HFD-induced ER stress by inhibiting glucose-regulated protein 78 (GRP78), protein kinase R like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) mRNA and protein expression. Mechanistically, phosphatidylcholine promoted CCTα protein expression to alleviate the obstruction of CMs synthesis and secretion caused by fatty acid (palmitic acid and oleic acid). Moreover, phosphatidylcholine enhanced the transcription of mttp and sar1b genes by PPARα through reducing the interaction between ATF4 and PPARα, thereby promoting the CMs assembly and secretion to alleviate fatty acid-induced lipid deposition in primary intestinal cells of yellow catfish. Overall, this study reveals that phospholipids alleviate HFD-induced intestinal lipid accumulation through the ATF4-PPARα-MTTP/SAR1B pathway, and provides strong basis for phospholipids in the prevention of obesity-related metabolic diseases.