Abstract
The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation.
Highlights
The intestine plays a prominent role in the biosynthesis of triacylglycerol
The activity of TAG synthesis coincides with the absorption of dietary fat along the length of the intestine, and it is more active in Triacylglycerol is an inert storage and transport molecule of fatty acids [1]
The goal of this review is to provide an overview of TAG synthesis in the intestine, focusing on recent findings supporting the idea that limiting the rate of TAG synthesis in the proximal intestine alters the kinetics of fat absorption and modulates systemic energy balance
Summary
Intestinal TAG synthesis occurs mainly after meals, as the primary source of substrates for intestinal TAG synthesis are digested fats taken up from the apical membranes of enterocytes [2]. In genetically engineered mice expressing different levels of MGAT2 in the intestine, the levels of MGAT activity determine the rate of MAG, but not fatty acid, uptake from the lumen into enterocytes in a cell-autonomous manner [36, 37] These findings suggest that MGAT-mediated esterification may facilitate MAG uptake by trapping MAG for DAG/TAG synthesis, consistent with the idea that intracellular metabolism promotes substrate uptake. Studies using mice deficient in either FABP support the proposition that IFABP channels fatty acids for TAG synthesis, while LFABP channels MAG for TAG synthesis and may be involved in fatty acid oxidation [41] These mice do not show overt fat malabsorption, indicating that either these FABPs play minor roles in fat absorption or their functions in the process can be compensated for when they are absent. The functions of ACSL5 likely can be compensated for by other ACSLs expressed in the intestine
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