Genetic Regulation of Intestinal Lipid Transport and Metabolism

Microbiome-Mediated Effects of the Mediterranean Diet on Inflammation

“…During digestion, TGs, the predominant form of dietary fat, are broken down into free fatty acids that enter enterocytes by free diffusion through the cellular membrane and by specific fatty acid transporters (43). These free fatty acids are then transported to the endoplasmic reticulum by fatty acid binding proteins where they are repackaged, along with cholesterol, fat-soluble vitamins, and LPSs, into prechylomicrons (43,44). The prechylomicron, stabilized by apolipoprotein B, is transported through the Golgi apparatus, preparing it for secretion from the cell into the lymphatic and eventually cardiovascular circulation (44).…”

“…These free fatty acids are then transported to the endoplasmic reticulum by fatty acid binding proteins where they are repackaged, along with cholesterol, fat-soluble vitamins, and LPSs, into prechylomicrons (43,44). The prechylomicron, stabilized by apolipoprotein B, is transported through the Golgi apparatus, preparing it for secretion from the cell into the lymphatic and eventually cardiovascular circulation (44). Whereas dietary lipids are absorbed mainly in the proximal small intestine, the majority of the GI microbiota, the largest source of LPSs in the body, is resident in the distal small intestine and colon.…”

Conditional hepatocyte ablation of PDIA1 uncovers indispensable roles in both APOB and MTTP folding to support VLDL secretion

“…Overproduction of hepatic VLDL is a common cause of hyperlipidemia in obesity and type II diabetes [ 2 , [4] , [5] , [6] , [7] ]. On the contrary, genetic defects in hepatic VLDL assembly and secretion cause metabolic dysfunction associated steatotic liver disease (MASLD) in mice and humans [ 6 , [8] , [9] , [10] , [11] , [12] , [13] , [14] ]. Recent clinical studies suggest that reduced hepatic VLDL secretion also contributes to MASLD progression to steatohepatitis (MASH) in obese subjects [ 15 , 16 ].…”

“…The biosynthesis of VLDL is generally believed to follow a two-step process occurring in the lumen of the endoplasmic reticulum (ER) [ 6 , 7 , 14 ]. The initial step involves the translocation of the nascent apolipoprotein B (APOB) polypeptide across the ER membrane and co-translational lipidation of APOB by the microsomal TG transfer protein (MTTP), leading to the formation of a primordial APOB particle [ 6 , 14 , 27 ].…”

“…The biosynthesis of VLDL is generally believed to follow a two-step process occurring in the lumen of the endoplasmic reticulum (ER) [ 6 , 7 , 14 ]. The initial step involves the translocation of the nascent apolipoprotein B (APOB) polypeptide across the ER membrane and co-translational lipidation of APOB by the microsomal TG transfer protein (MTTP), leading to the formation of a primordial APOB particle [ 6 , 14 , 27 ]. The second step involves the bulk addition of TG to VLDL and chylomicron precursors in the smooth ER [ 6 , 7 , 14 , 28 ] and to a lesser extent in the Golgi apparatus [ 6 , 29 , 30 ], through the fusion of pre-VLDL/chylomicron particles with luminal lipid droplets in these secretory compartments.…”