Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion

Okawa, Mayumi; Fujii, Kenji; Ohbuchi, Katsuya; Okumoto, Mayumi; Aragane, Katsumi; Sato, Hiromu; Tamai, Yoshitaka; Seo, Toru; Itoh, Yoshiki; Yoshimoto, Ryo

doi:10.1016/j.bbrc.2009.08.167

Cited by 63 publications

(79 citation statements)

References 31 publications

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“…Ϫ / Ϫ and wild-type mice ( 17,35 ). Because both its substrate monoacylglycerols and its product diacylglycerols can serve as signaling within the four diet strata using the mixed-effects model as well as using a ratio method adjusting for body weight ( Figs.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain

Nelson

Gao

Spencer

et al. 2011

Journal of Lipid Research

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for assimilation and thus exert a lower thermic effect of food (diet-induced thermogenesis) (3)(4)(5). Individuals that assimilate dietary fat effi ciently to meet their needs between meals have an advantage in enduring starvation. Thus, genes conferring this trait may be selected through evolution. During times of continuous abundance, however, individuals thrifty of energy substrates and high in metabolic effi ciency are prone to accumulating fuel surpluses in adipose and other tissues ( 6, 7 ). In humans, excessive fat accumulation is associated with metabolic diseases, including obesity, hepatic steatosis, and insulin resistance, which plague many industrialized parts of the world ( 8, 9 ).The absorption of dietary fat involves the resynthesis of digested triacylglycerol in enterocytes, mainly through a pathway catalyzed by acyl CoA:monoacylglycerol acyltransferase (MGAT) ( 10 ). Three related genes have been identifi ed that code for MGAT; among them, only Mogat2 is highly expressed in the small intestine of both mice and humans ( 11-15 ). Thus, Mogat2 probably encodes the intestinal MGAT activity, although Mogat3 is also found in the distal intestine in humans ( 14 ).Consistent with a role of MGAT2 in promoting conservation of dietary fat, mice lacking the enzyme ( Mogat2 Ϫ / Ϫ ) are resistant to obesity and other metabolic disorders induced by high-fat feeding ( 16,17 ؊ / ؊ mice expended energy and lost weight like wild-type controls. To determine whether MGAT2 defi ciency protects against obesity in the absence of high-fat feeding, we crossed Mogat2 ؊ / ؊ mice with genetically obese Agouti mice. MGAT2 defi ciency increased energy expenditure and prevented these mice from gaining excess weight. Our results suggest that MGAT2 modulates energy expenditure through multiple mechanisms, including one independent of dietary fat; these fi ndings also raise the prospect of inhibiting MGAT2 as a strategy for combating obesity and related metabolic disorders resulting from excessive calorie intake. Abbreviations: DGAT, diacylglycerol acyltransferase; MGAT, monoacylglycerol acyltransferase; RER, respiratory exchange ratio.

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Section: Discussionmentioning

confidence: 99%

Deficiency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain

Nelson

Gao

Spencer

et al. 2011

Journal of Lipid Research

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“…Since very little is known about the apparent mechanism of fat-stimulated GIP secretion, we hypothesized that fat-induced GIP secretion may be triggered by intestinal fatty acid transport. Previous studies indicated that fat-stimulated GIP secretion was associated with chylomicron formation (26,35). Either chylomicron formation (24) or fatty acid uptake (23) was shown to be mediated by fatty acid translocase (FAT)/CD36 in the proximal intestine.…”

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confidence: 99%

Dietary 1-monoolein decreases postprandial GIP release by reducing jejunal transport of glucose and fatty acid in rodents

Shimotoyodome

Osaki

Onizawa

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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-Postprandial secretion of insulin and glucose-dependent insulinotropic polypeptide (GIP) is differentially regulated by not only dietary carbohydrate but also fat. Recent studies have shown that the ingestion of diacylglycerol (DAG) results in lower postprandial insulin and GIP release than that of triacylglycerol (TAG), suggesting a possible mechanism for the antiobesity effect of DAG. The structural and metabolic characteristics of DAG are believed to be responsible for its beneficial effects. This study was designed to clarify the effect of 1-monoacylglycerol [oleic acid-rich (1-MO)], the characteristic metabolite of DAG, on postprandial insulin and GIP secretion, and the underlying mechanism. Dietary 1-MO dose dependently stimulated whole body fat utilization, and reduced high-fat diet-induced body weight gain and visceral fat accumulation in mice, both of which are consistent with the physiological effect of dietary DAG. Although glucose-stimulated insulin and GIP release was augmented by the addition of fat, coingestion of 1-MO reduced the postprandial hormone release in a dose-dependent manner. Either glucose or fatty acid transport into the everted intestinal sacs and enteroendocrine HuTu-80 cells was also reduced by the addition of 1-MO. Reduction of either glucose or fatty acid transport or the nutrient-stimulated GIP release by 1-MO was nullified when the intestine was pretreated with sodium-glucose cotransporter-1 (SGLT-1) or fatty acid translocase (FAT)/CD36 inhibitor. We conclude that dietary 1-MO attenuates postprandial GIP and insulin secretion by reducing the intestinal transport of the GIP secretagogues, which may be mediated via SGLT-1 and FAT/CD36. Reduced secretion of these anabolic hormones by 1-MO may be related to the antiobesity effect of DAG.FAT/CD36; indirect calorimetry; insulin; intestinal transport; SGLT-1 THE WIDESPREAD PREVALENCE of obesity is now a worldwide health problem. Excess adiposity, especially excess abdominal fat accumulation, increases the risk of morbidity from a number of diseases, including diabetes, hypertension, and cardiovascular diseases and is also associated with a greater risk for certain cancers (25). Therefore, improvement of lifestyle, particularly dietary content, is often recommended for the primary prevention and treatment of these diseases. Diacylglycerol (DAG), which consists of 1,3-DAG and 1,2(2,3)-DAG is contained in natural edible oils at a level of 2-10% (8) and is consumed in the daily human diet. Prior studies in animals and humans have shown that dietary DAG oil composed mainly of 1,3-DAG leads to the suppression of body fat accumulation, body weight loss, improved glucose tolerance, and lower postprandial lipemia compared with that of triacylglycerol (TAG), which has a similar fatty acid composition (32, 39). Recent studies have shown that the ingestion of a 1,3-DAG-rich diet results in a lower postprandial insulin response than that of TAG oil in humans (33, 40). Since a high-level postprandial insulin response has been shown to be associate...

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“…In fact, MGAT2 KO mice demonstrate reduced fat uptake in the small intestine and delay in the absorption of fat into circulation [105]. In addition, the elevation of postprandial GLP-1 and not PYY levels are observed in MGAT2 KO mice fed a HF diet [106].…”

Section: Acyl-coa: Monoacylglycerol Acyltransferase 2 Inhibitormentioning

confidence: 99%

Usefulness of Obese Animal Models in Antiobesity Drug Development

Ohta¹,

Murai²,

Yamada³

2017

Adiposity - Omics and Molecular Understanding

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Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion

Cited by 63 publications

References 31 publications

Deficiency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain

Deficiency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain

Dietary 1-monoolein decreases postprandial GIP release by reducing jejunal transport of glucose and fatty acid in rodents

Usefulness of Obese Animal Models in Antiobesity Drug Development

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