Triglyceride absorption

In 1987, scientists at Hoffmann-La Roche described their discovery of hpstatin (5), a secondary metabolite isolated from Strptomyces toxytricini, and demonstrated that it is a potent inhibitor of pancreatic lipase.Simple hydrogenation of 5 formed terahydrolipstatin (1,USAN, orlistat) which possesses comparable biological activity but is more stable than 5. Orlistat (1, Xenical ) works through pancreatic lipase inhibition. Pancreatic lipase is the key enzyme of dietary triglyceride absorption, exerting its activity... 

Ikeda, I., Tomari, Y., and Sugano, M. 1989b. Interrelated effects of dietary fiber and fat on lymphatic cholesterol and triglyceride absorption in rats. J. Nutr. 119, 1383-1387. 

Thus, in summary, it may be concluded that much of the cholesterol synthesized in the intestine is apparently used for local purposes. Under circumstances where there is no triglyceride absorption taking place essentially no newly synthesized sterol of intestinal origin can be detected in the lymphatic outflow from the gut. During active triglyceride absorption, however, the rate of sterol synthesis increases markedly in the intestinal absorptive cells, and a portion of this newly synthesized cholesterol is incorporated into chylomicrons and other intestinal lipoproteins and delivered into the lymph. Thus, both the rate of sterol synthesis by the intestine and the rate of entry of this sterol into the body pools is partially dictated by the rate of triglyceride absorption. 

The relative importance of each of these contributions to pool C is likely to be different in epithelial cells located at different points along the villus-crypt axis. The fact that cholesterol derived from synthesis and from the uptake of LDL is critically important for membrane formation and differentiation is suggested by the finding that 70-80% of total mucosal sterol synthetic activity and LDL transport activity are localized to the immature cells of the lower villus and crypt regions in both the proximal and distal intestine. In the mature absorptive cells of the upper villus in the jejunum, where most sterol absorption takes place, the rate of cholesterol synthesis appears to be suppressed. In the absence of fat absorption, cholesterol newly synthesized in these cells apparently is sloughed into the lumen and not reabsorbed. However, with active triglyceride absorption cholesterol synthesis in these cells is increased and a portion of this sterol appears in the intestinal lymph. Only under this condition does pool B apparently supply sterol for lipoprotein formation. 

Recent data indicate that ezetimibe inhibits a specific transport process in jejunal enterocytes, which take up cholesterol from the lumen. The putative transport protein is Niemann-Pick Cl-hke 1 protein (NPCILI). In wild-type mice, ezetimibe inhibits cholesterol absorption by about 70% in NPCILI knockout mice, cholesterol absorption is 86% lower than in wild-type mice, and ezetimibe has no effect on cholesterol absorption. Ezetimibe does not affect intestinal triglyceride absorption. In human subjects, ezetimibe reduced cholesterol absorption by 54%, precipitating a compensatory increase in cholesterol synthesis, which can be inhibited with a cholesterol synthesis inhibitor such as a statin. There is also a substantial reduction of plasma levels of plant sterols (campesterol and sitosterol concentrations are reduced by 48 and 41%, respectively), indicating that ezetimibe also inhibits intestinal absorption of plant sterols. 

Sugiyama H, Akazome Y, Shoji T, et al. Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and triglyceride absorption. / Agric Food Chan. 2007 55(11) 4604—4609. 

Pfluger (1901), put forward the hypothesis that the complete hydrolysis of glycerides by pancreatic lipase was an essential step in triglyceride absorption. The lipolytic theory , was further advanced by Verzar and McDougal (1936), who also demonstrated the hydrotropic action of bile salts, which causes the solubilization of fatty acids and enables them to cross the intestinal barrier. This theory requires also the resynthesis of the triglycerides in the intestinal cells, to... 

The processes involved in triglyceride absorption may be summarized in the following scheme. 

Fig. 6. Scheme of triglyceride absorption. Hatched blocks indicate site(s) of possible lesion in a-/8-lipo-... 

Although the rate-limiting step in cholesterol and triglycerides absorption has not been clearly identified, a number of experimental... 

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