The Acyl CoenzymeA:Monoacylglycerol Acyltransferase 3 (MGAT3) Gene is a Pseudogene in Mice but Encodes a Functional Enzyme in Rats

Yue, Yong; Chen, Yanqun; Zhang, Youyan; Wang, He; Qian, Yue‐Wei; Arnold, Jeffrey S.; Calley, John N.; Li, Shuyu D.; Perry, William L.; Zhang, Hong Y.; Konrad, Robert J.; Cao, Guoqing

doi:10.1007/s11745-011-3537-1

Cited by 30 publications

(30 citation statements)

References 25 publications

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“…The present study also suggests the importance of MOGAT3 , which is not analogous to murine Mogat3 , to hepatic MGAT activity. In fact, the mouse Mogat3 gene is a pseudogene ( 12 ). We also detected high expression of MOGAT in human liver, which is in close agreement with other reports (8)(9)(10)(11) and in contrast to the expression profi le in murine species.…”

Section: Mogat Gene Expression Is Diminished Following Marked Weight supporting

confidence: 92%

“…However, the human and murine MOGAT3 / Mogat3 genes are not analogs and evolved separately in postspeciation duplication events. The murine Mogat3 gene arose from duplication of Mogat2 , whereas the human MOGAT3 gene may have arisen from duplication of the gene encoding DGAT2 ( 12 ). Human MGAT3 also possesses signifi cant DGAT activity and can catalyze both reactions required to convert monoacylglycerol to TAG ( 13 ).…”

Section: Study Subjectsmentioning

confidence: 99%

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Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver

Hall

Kou

Chen

et al. 2012

Journal of Lipid Research

100

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Obesity is associated with nonalcoholic fatty liver disease (NAFLD), which represents a spectrum of liver abnormalities that are characterized by an increase in intrahepatic triacylglycerol (TAG) content (i.e., steatosis) with or without infl ammation and fi brosis (i.e., steatohepatitis). The presence of steatosis is an important marker of metabolic dysfunction and correlates closely with multiorgan insulin resistance and dyslipidemia ( 1 ), which are key risk factors for diabetes and coronary artery disease. However, the mechanisms responsible for the link between increased intrahepatic TAG content and metabolic disease are not clear.It has been hypothesized that the hepatocellular accumulation of specifi c lipid intermediates, including diacylglycerol (DAG), acyl-CoA, and ceramide, in people with NAFLD is the molecular mechanism driving insulin resistance ( 2, 3 ). Accordingly, an understanding of the metabolic interrelationships among hepatic glycerolipid synthesis and lipid intermediates has important physiological and clinical implications. There are two pathways for diacylglycerol synthesis. In the liver, most DAG and TAG are synthesized from the sequential acylation of glycerol-3-phosphate. However, these lipids can also be synthesized from monoacylglycerol through the monoacylglycerol acyltransferase (MGAT) pathway ( Fig. 1 ) ( 4, 5 ). The MGAT and glycerol-3-phosphate pathways are convergent and each results in the synthesis of DAG, which is then acylated to form TAG by the DAG acyltransferase (DGAT) enzymes ( Fig. 1 ). The MGAT pathway is an important TAG Abstract Intrahepatic lipid accumulation is extremely common in obese subjects and is associated with the development of insulin resistance and diabetes. Hepatic diacylglycerol and triacylglycerol synthesis predominantly occurs through acylation of glycerol-3-phosphate. However, an alternative pathway for synthesizing diacylglycerol from monoacylglycerol acyltransferases (MGAT) could also contribute to hepatic glyceride pools. MGAT activity and the expression of the three genes encoding MGAT enzymes ( MOGAT1 , MOGAT2 , and MOGAT3 ) were determined in liver biopsies from obese human subjects before and after gastric bypass surgery. MOGAT expression was also assessed in liver of subjects with nonalcoholic fatty liver disease (NAFLD) or control livers. All MOGAT genes were expressed in liver, and hepatic MGAT activity was readily detectable in liver lysates. The hepatic expression of MOGAT3 was highly correlated with MGAT activity, whereas MOGAT1 and MOGAT2 expression was not, and knockdown of MOGAT3 expression attenuated MGAT activity in a liver-derived cell line. Marked weight loss following gastric bypass surgery was associated with a signifi cant reduction in MOGAT2 and MOGAT3 expression, which were also overexpressed in NAFLD subjects. These data suggest that the MGAT pathway is active and dynamically regulated in human liver and could be an important target for pharmacologic intervention for the treatment of obesity-related insulin resistance and ...

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Section: Mogat Gene Expression Is Diminished Following Marked Weight supporting

confidence: 92%

Section: Study Subjectsmentioning

confidence: 99%

Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver

Hall

Kou

Chen

et al. 2012

Journal of Lipid Research

100

View full text Add to dashboard Cite

show abstract

“…While Mogat1 and Mogat2 are present in both humans and rodents, expression of Mogat3 has only been observed in rats and in humans, but not in mice, where it is shown to be a pseudogene ( 18 ). Based on conservation of Mogat1 and Mogat2 in rats and humans, it seems unlikely that mice lack an active Mogat3 .…”

mentioning

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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“…MGAT enzymes catalyze the acylation of MAG to DAG, which is the direct precursor of TAG. In higher organisms, a family of three related genes (Mogat1, Mogat2, and Mogat3) encoding enzymes with MGAT activity has been identified, but the mouse Mogat3 is a pseudogene (5).…”

mentioning

confidence: 99%

Inhibiting Monoacylglycerol Acyltransferase 1 Ameliorates Hepatic Metabolic Abnormalities but Not Inflammation and Injury in Mice

Soufi

Hall

Chen

et al. 2014

Journal of Biological Chemistry

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Background: Mogat1 inhibition improves glucose metabolism in obese mice, but its effects on liver injury are unknown. Results: Mogat1 knockdown improved hepatic metabolic abnormalities but did not reduce liver inflammation or injury. Conclusion: Hepatic injury and metabolic abnormalities are separable disease entities. Significance: Attention to liver injury markers should be made when evaluating metabolic therapies.

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The Acyl CoenzymeA:Monoacylglycerol Acyltransferase 3 (MGAT3) Gene is a Pseudogene in Mice but Encodes a Functional Enzyme in Rats

Cited by 30 publications

References 25 publications

Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver

Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver

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

Inhibiting Monoacylglycerol Acyltransferase 1 Ameliorates Hepatic Metabolic Abnormalities but Not Inflammation and Injury in Mice

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