No abstract

Dietary triacylglycerols are a major source of energy for animals. The absorption of dietary triacylglycerols involves their hydrolysis to free fatty acids and monoacylglycerols in the intestinal lumen, the uptake of these products into enterocytes, the resynthesis of triacylgylcerols, and the incorporation of newly synthesized triacylglycerols into nascent chylomicrons for secretion. In enterocytes, the final step in triacylglycerol synthesis is believed to be catalyzed primarily through the actions of acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. In this study, we analyzed intestinal triacylglycerol absorption and chylomicron synthesis and secretion in DGAT1-deficient (Dgat1 ؊/؊ ) mice. Surprisingly, DGAT1 was not essential for quantitative dietary triacylglycerol absorption, even in mice fed a high fat diet, or for the synthesis of chylomicrons. However, Dgat1 ؊/؊ mice had reduced postabsorptive chylomicronemia (1 h after a high fat challenge) and accumulated neutrallipid droplets in the cytoplasm of enterocytes when chronically fed a high fat diet. These results suggest a reduced rate of triacylglycerol absorption in Dgat1 mice. Analysis of intestine from Dgat1؊/؊ mice revealed activity for two other enzymes, DGAT2 and diacylglycerol transacylase, that catalyze triacylglycerol synthesis and apparently help to compensate for the absence of DGAT1. Our findings indicate that multiple mechanisms for triacylglycerol synthesis in the intestine facilitate triacylglycerol absorption.The absorption of triacylglycerols by the intestine is highly efficient, and more than 95% of dietary triacylglycerols is absorbed, even if the diet is rich in fat. By comparison, only 30 -70% of dietary cholesterol is absorbed in most animals (1). The high efficiency of triacylglycerol absorption is likely due to an evolutionary pressure that maximized the ability to absorb rich sources of energy (such as fat) when food sources were scarce.Intestinal triacylglycerol absorption occurs by a series of steps in which dietary triacylglycerols are first hydrolyzed in the intestinal lumen and then resynthesized within enterocytes. In the lumen, dietary triacylglycerols are hydrolyzed by lipases to generate free fatty acids and monoacylglycerols. These molecules are taken up by enterocytes and then enter the triacylglycerol biosynthesis pathways. The triacylglycerol products are incorporated into nascent chylomicrons, which are subsequently secreted from enterocytes and enter the lymphatic system.Triacylglycerol biosynthesis in the intestine is believed to occur mainly through the monoacylglycerol pathway. In this pathway, monoacylglycerol and fatty acyl-CoA are covalently joined to form diacylglycerol in a reaction catalyzed by monoacylglycerol acyltransferase (MGAT) 1 (2). Diacylglycerol and fatty acyl-CoA are then used to synthesize triacylglycerol in a reaction catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. High levels of DGAT activity are present in the small intestine (3-5), and both known DGAT genes, Dgat1...

Increased production of reactive oxygen species is a feature of most, if not all, human disease, including cardiovascular disease and cancer. Dietary antioxidants may be especially important in protecting against human diseases associated with free radical damage to cellular DNA, lipids, and proteins. Ascorbic acid is an effective water-soluble antioxidant, and epidemiologic studies suggest that increased ascorbate nutriture is associated with reduced risk of some degenerative diseases, especially cancer and eye cataracts. Population studies have also shown that high vitamin E intakes are associated with decreased risk of coronary heart disease, possibly as a result of inhibition of atherogenic forms of oxidized low-density lipoprotein. Recent data suggest that beta-carotene provides protection against lipid peroxidation in humans, as well as provitamin A activity. Yet, present data are not sufficient to quantitate micronutrient requirements needed to protect against oxidative damage. The antioxidant roles of many food constituents, such as polyphenols, have not been clarified. Most antioxidants can act as prooxidants under certain conditions, and more research is needed to determine the occurrence and importance of this in vivo. The few controlled intervention trials carried out so far have shown mixed results as to the potential of antioxidant supplements for reducing the incidence of chronic diseases. Definitive recommendations on antioxidant intakes for disease prevention must await evidence from controlled studies and intervention trials, some currently in progress. Overall, the present data suggest that protection against oxidative damage and related disease is best served by the variety of antioxidant substances found in fruit and vegetables.