Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism

Abstract

cell membranes. The biosynthesis of TAG thus serves many physiological functions. Because it is highly reduced and anhydrous, TAG is the primary energy substrate stored in adipose tissues to sustain animals during fasting. TAG is also synthesized in the liver for the assembly and secretion of VLDL to transport neutral lipids to other tissues, as well as in the mammary gland for the formation of milk fat globules to deliver fatty acids and other lipid-soluble nutrients to mammalian neonates.In the intestine, TAG synthesis is prominent for its role in the absorption of dietary fat ( 2, 3 ). TAG forms the bulk of animal fats and plant oils. It accounts for approximately 95% of dietary fat, depending on the food sources, with the rest as phospholipids and trace amounts of sterols, lipid-soluble vitamins, and other lipophilic components. Because of its hydrophobicity, TAG does not traverse the cellular membrane. Its absorption involves hydrolysis to fatty acids and monoacylglycerol (MAG) in the intestinal lumen, lipid uptake by the enterocytes, resynthesis of TAG, and assembly and secretion of ApoB-containing chylomicrons for delivery of TAG and other lipid-soluble nutrients. Like with most nutrients, the absorption of TAG occurs mostly in the proximal half of the intestine and less so in the distal intestine, where specifi c compounds, such as bile acids and vitamin B12, are absorbed. The activity of TAG synthesis coincides with the absorption of dietary fat along the length of the intestine, and it is more active in Press, September 17, 2014 DOI 10.1194 Abbreviations: ACSL, acyl-CoA synthetase; AGPAT, 1-acylglycerol-3-phosphate acyltransferase; ATGL, adipose triglyceride lipase; CD36, cluster of differentiation; CGI-58, comparative gene identifi cation-58; Cideb, cell death-inducing DNA fragmentation factor 45 (DFF45) -like effector b; DAG, diacylglycerol; DGAT, acyl-CoA:diacylglycerol acyltransferase; ER, endoplasmic reticulum; FABP, fatty acid binding protein; GLP-1, glucagon-like peptide 1; GPAT, glycerol-3-phosphate acyltransferase; G3P, glycerol-3-phosphate; IFABP, intestine-type fatty acid binding protein; LFABP, liver-type fatty acid binding protein; MAG, monoacylglycerol; MBOAT, membrane-bound O-acyltransferase; MGAT, acylCoA:monoacylglycerol acyltransferase; MTP, microsomal triacylglycerol transfer protein; PA, phosphatidic acid; PAP, phosphatidic acid phosphatase; TAG, triacylglycerol (triglyceride ). Published, JLR Papers in

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“…MGAT2 has been suggested as playing an important role in dietary fat absorption in the intestine (Grigor and Bell, 1982;Yen and Farese, 2003;Yen et al, 2014). We therefore first evaluated the rate of fat absorption after a single dose of JTP-103237.…”

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol

“…MGAT2 is exclusively expressed in the intestine, where the MGAT pathway accounts for ;75% of TG synthesis (109), and MGAT plays an important role in dietary lipid absorption. DGAT1 is abundantly expressed in the small intestine (110). DGAT1 inhibition reduced postprandial TG plasma excursion in humans; however, this was accompanied by gastrointestinal side effects (111).…”

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“…In the small intestine, the majority of TAG is derived from esterification of fatty acids to monoacylglycerol, which is abundant in the intestinal lumen as a result of hydrolysis of dietary lipids [20,21]. Excellent reviews have focused on the monoacylglycerol pathway [22,23], and here, we will focus largely on the glycerol 3-phosphate pathway, which is active in most tissue types.…”