Intestine-specific Deletion of Acyl-CoA:Monoacylglycerol Acyltransferase (MGAT) 2 Protects Mice from Diet-induced Obesity and Glucose Intolerance

Nelson, David W.; Gao, Yu Tang; Yen, Mei‐I; Yen, Chi‐Liang Eric

doi:10.1074/jbc.m114.555961

Cited by 75 publications

(94 citation statements)

References 43 publications

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“…Ϫ / Ϫ mice was measured using tissue homogenates, as previously described ( 16,27 ). Reactions were started by adding homogenates to the assay mixture and were stopped after 5 min by adding chloroform:methanol (2:1, v:v ).…”

Section: In Vitro Mgat Assaysmentioning

confidence: 99%

Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2−/−) or obese (ob/ob) mice

Agarwal

Tunison

Dalal

et al. 2016

Journal of Lipid Research

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Section: In Vitro Mgat Assaysmentioning

confidence: 99%

Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2−/−) or obese (ob/ob) mice

Agarwal

Tunison

Dalal

et al. 2016

Journal of Lipid Research

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“…The underlying physiological mechanisms involve a transient decrease in food intake and a persistent increase in energy expenditure ( 7,8 ). Unexpectedly, the increase in energy expenditure does not require high-fat feeding, and MGAT2 defi ciency also protects Agouti mice from excess weight gain ( 9 ).…”

mentioning

confidence: 99%

“…Interestingly, these Mogat2 Ϫ / Ϫ mice absorb a normal quantity of fat but are protected from obesity and other metabolic disorders induced by high-fat feeding. The underlying physiological mechanisms involve a transient decrease in food intake and a persistent increase in energy expenditure ( 7,8 ). Unexpectedly, the increase in energy expenditure does not require high-fat feeding, and MGAT2 defi ciency also protects Agouti mice from excess weight gain ( 9 ).…”

mentioning

confidence: 99%

Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase 2 protects mice from diet-induced obesity and glucose intolerance

Banh¹,

Nelson²,

Gao

et al. 2015

Journal of Lipid Research

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ids and metabolic energy. TAG synthesis in most cells starts with acylation of glycerol-3-phosphate, followed by two additional acylation steps, whereas in some cells it uses monoacylglycerol (MAG) as the initial acyl acceptor. AcylCoA:monoacylglycerol acyltransferase (MGAT) catalyzes the latter pathway and generates diacylglycerol for the fi nal acylation step ( 1 ). As MAG is mostly a degradation product of TAG, the MGAT pathway is thought to be important for recycling of TAG. Indeed, the best-characterized MGAT function is in the absorption of dietary fat. During the process, dietary TAG is hydrolyzed in the intestinal lumen to MAG and fatty acids. After uptake, the hydrolysis products are resynthesized to TAG in enterocytes for the assembly of chylomicron, which in turn delivers dietary lipids to peripheral tissues ( 2 ).Among three identifi ed genes encoding MGAT enzymes, Mogat2 is highly expressed in the intestine of both rodents and humans ( 3-6 ). Supporting the role of MGAT2 as an intestinal MGAT mediating fat absorption, constitutive global inactivation of the enzyme, through germ-line transmission of a null mutation in Mogat2 , greatly reduces intestinal MGAT activity and delays fat absorption ( 7 ). Interestingly, these Mogat2 Ϫ / Ϫ mice absorb a normal quantity of fat but are protected from obesity and other metabolic disorders induced by high-fat feeding. The underlying physiological mechanisms involve a transient decrease in food intake and a persistent increase in energy expenditure ( 7,8 ). Unexpectedly, the increase in energy expenditure does not require high-fat feeding, and MGAT2 defi ciency also protects Agouti mice from excess weight gain ( 9 ). Findings from both gain-and loss-of-function mouse models indicate that MGAT2 in the intestine is a major contributor but incompletely accounts for the Abstract Acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 catalyzes triacylglycerol (TAG) synthesis, required in intestinal fat absorption. We previously demonstrated that mice without a functional MGAT2-coding gene ( Mogat2) exhibit increased energy expenditure and resistance to obesity induced by excess calories. One critical question raised is whether lacking MGAT2 during early development is required for the metabolic phenotypes in adult mice. In this study, we found that Mogat2 ؊ / ؊ pups grew slower than wildtype littermates during the suckling period. To determine whether inactivating MGAT2 in adult mice is suffi cient to confer resistance to diet-induced obesity, we generated mice with an inducible Mogat2 -inactivating mutation. Mice with adult-onset MGAT2 defi ciency ( Mogat2 AKO ) exhibited a transient decrease in food intake like Mogat2 ؊ / ؊ mice when fed a high-fat diet and a moderate increase in energy expenditure after acclimatization. They gained less weight than littermate controls, but the difference was smaller than that between wild-type and Mogat2 ؊ / ؊ mice. The moderate reduction in weight gain was associated with reduced hepatic TAG and improved glucose tolerance. Similar pr...

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“…Moreover, MGAT2 deficiency results in increased metabolic rates, decreased food consumption, and protection from obesity in genetically obese Agouti mice, suggesting that MGAT2 regulates energy balance [106,107]. The intestinal function of MGAT2 and the effect of this function on obesity are also investigated using intestine-specific MGAT2 KO mice [108]. Intestinal-specific deletion of MGAT2 alters TG metabolism in the small intestine and delays fat absorption.…”

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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Intestine-specific Deletion of Acyl-CoA:Monoacylglycerol Acyltransferase (MGAT) 2 Protects Mice from Diet-induced Obesity and Glucose Intolerance

Cited by 75 publications

References 43 publications

Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2−/−) or obese (ob/ob) mice

Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2−/−) or obese (ob/ob) mice

Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase 2 protects mice from diet-induced obesity and glucose intolerance

Usefulness of Obese Animal Models in Antiobesity Drug Development

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