Regulation of triglyceride biosynthesis in adipose and intestinal tissue

Polheim, Diether; David, J.S.K.; Schultz, F. Michael; Wylie, Mary Bob; Johnston, John M.

doi:10.1016/s0022-2275(20)36874-7

Cited by 75 publications

(5 citation statements)

References 25 publications

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“…The relative importance of the MG-pathway and the alpha-glycerophosphate pathway depends on the supply of 2-MG and FA. During normal lipid absorption, when 2MG is sufficiently present, the 2-MG pathway facilitates the conversion of 2-MG and FA to form TG and aids in inhibiting the alpha-glycerophosphate pathway (193,194,204). Conversely, when the supply of 2-MG is lacking or insufficient, the alpha-glycerophosphate pathway becomes the major pathway for the formation of TG.…”

Section: Monoglycerides and Fatty Acidmentioning

confidence: 99%

Intestinal lipid absorption and transport

Phan

Tso²

2001

Front Biosci

166

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The purpose of this review is to update the reader on our current knowledge of the digestion, uptake, and transport of dietary lipid. In particular, it discusses how intestinal lipid transporters may play a role in the uptake of lipids by the enterocytes, and how chylomicrons are formed in the enterocytes and packaged for export into the lymphatic system through exocytosis. The classification and properties of lipids is first described followed by a discussion of structured lipids and their role in human nutrition. Digestion of triacylglycerols takes place in the stomach aided by the enzyme gastric lipase. The origin and properties of lingual and gastric lipase are reviewed. Most digestion of triacylglycerols by pancreatic lipase occurs in the intestinal lumen. Similarly, digestion of cholesteryl ester and phospholipids also takes place in the intestinal lumen. This review describes in considerable detail the uptake of lipid digestion products by the enterocytes, particularly the role of recently identified lipid transporters. The intracellular trafficking and the resynthesis of complex lipids from the lipid digestion products are talked about, particularly within the context of the recently generated knockout mouse that lacks the key lipid reesterification enzymes. Finally, the mechanisms of the formation and secretion of chylomicrons is described and clinical disorders discussed.

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Section: Monoglycerides and Fatty Acidmentioning

confidence: 99%

Intestinal lipid absorption and transport

Phan

Tso²

2001

Front Biosci

166

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“…most important phospholipids, phosphatidylcholine and phosphatidylethanolamine (Hjelmstad & Bell, 1991a). Further, MGAT's ín-2-monoacylglycerol substrate is a competitive inhibitor of glycerol-3-phosphate acyltransferase, the committed step in glycerolipid biosynthesis (Polheim et al, 1973;Coleman, 1988), and diacylglycerol kinase, a major attenuator of sn-1,2-diacylglycerol signals (Bishop et al, 1986). An increase in the concentration of cellular monoacylglycerol might, therefore, inhibit the glycerol 3-phosphate pathway of glycerolipid synthesis, and prolong the ability of sn-1,2-diacylglycerol to activate protein kinase C. In the intestine, MGAT provides the major pathway for the resynthesis of triacylglycerol and is critical for the assembly of chylomicra.…”

mentioning

confidence: 99%

Sphingosine Inhibits Rat Hepatic Monoacylglycerol Acyltransferase in Triton X-100 Mixed Micelles and Isolated Hepatocytes

Wang¹,

Coleman²

1995

Biochemistry

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Hepatic monoacylglycerol acyltransferase (MGAT), a developmentally-regulated microsomal activity that catalyzes the synthesis of sn-1,2-diacylglycerol, is regulated by anionic phospholipids and sn-1,2-diacylglycerol in Triton X-100 mixed micelles. Spingomyelin stimulated MGAT activity, whereas sphingosine, sphinganine, phytosphingosine, and stearylamine were inhibitors (IC50 of 9, 5.5, 5, and 6 mol %, respectively). Since ceramide and octylamine had relatively little effect, inhibition appears to require a free amino group and a long-chain hydrocarbon. Inhibition by sphingosine was competitive with respect to phosphatidic acid, phosphatidylinositol, or phosphatidylserine, suggesting that anionic phospholipids may activate MGAT at a specific site that is competitively blocked by sphingolipids. Both sphingosine and sphinganine inhibited MGAT activity in cultured hepatocytes from 10-day-old rats in a dose-dependent manner. Stimulation of MGAT activity by diacylglycerol was specific for sn-1,2-stereoisomers that contained two long fatty acyl chains. The diacylglycerol analogs phorbol 12-myristyl 13-acetate and ceramide had no effect. The highly cooperative activation of MGAT by sn-1,2-diacylglycerol was also inhibited by sphingosine. It is unlikely that activation of MGAT by low molar concentrations of anionic phospholipids is solely due to electrostatic interactions between the enzyme and negatively charged lipids because high ionic strength, neomycin, and Ca2+ had similar effects on enzyme activity irrespective of the presence or absence of phosphatidic acid. These data suggest that MGAT activity may be regulated physiologically by specific intermediates of glycerolipid metabolism and that, in neonatal rat liver, signal transduction may be linked to the synthesis of complex lipids via the monoacylglycerol pathway.

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“…Briefly, dietary triacylglycerol (TG) is hydrolysed in the small intestine, primarily by the activity of pancreatic lipase, to yield fatty acids, derived from cleavage at the sn-1/3 positions, and sn-2 monoacylglycerol (2-MG) [3] which are absorbed from the unstirred water layer interface between the gut lumen and the apical surface of enterocytes. Fatty acids and 2-MG derived from hydrolysed TG are reesterified in enterocytes to form primarily TG [4] or phosphatidylcholine (PC) before assembly into chylomicrons. In human enterocytes, between 70% and 90% of TG is synthesised via the MG pathway during the postprandial period [5], while the remainder is formed by the glycerol-3-phosphate pathway [4,6].…”

Section: Introductionmentioning

confidence: 99%

“…Fatty acids and 2-MG derived from hydrolysed TG are reesterified in enterocytes to form primarily TG [4] or phosphatidylcholine (PC) before assembly into chylomicrons. In human enterocytes, between 70% and 90% of TG is synthesised via the MG pathway during the postprandial period [5], while the remainder is formed by the glycerol-3-phosphate pathway [4,6]. Enterocytes synthesise PC by the CDP:phosphocholine cytidylyltransferase pathway [7,8] and by re-acylation of biliary lysoPC [7,8].…”

Section: Introductionmentioning

confidence: 99%