Role of Monoacylglycerol Acyltransferase-1 and Monoacylglycerol Acyltransferase-2 in Adipocyte Lipid Metabolism
Date
2019-01-07
Authors
Journal Title
Journal ISSN
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Publisher
ORCID
Type
Thesis
Degree Level
Masters
Abstract
Adipose tissue is the main storage site of triacylglycerol which provides energy to other tissues by producing fatty acids during fasting. Any dysregulation in triacylglycerol synthesis and breakdown in adipocytes can be responsible for obesity, diabetes, cardiovascular diseases and so on. The sequential acylation of glycerol-3-phosphate to produce triacylglycerol is well studied in adipocytes, whereas little is known about the role of the monoacylglycerol pathway in adipocyte triacylglycerol metabolism. Two monoacylglycerol acyltransferase (MGAT) isoforms, MGAT1 and MGAT2, have been found in serving the substrate-diacylglycerol for diacylglycerol acyltransferase (DGAT) to produce triacylglycerol in liver and intestine, respectively, but their roles in adipocyte lipid metabolism are not clear. We hypothesize that one or both of these MGAT enzymes contribute to adipose tissue triacylglycerol metabolism.
We used 3T3-L1 pre-adipocytes which can differentiate to adipocytes within 10 days by adding proper differentiation media. To explore the role of MGAT1 and MGAT2 in adipocytes, we used shRNA to knockdown MGAT1 or MGAT2 separately in pre-adipocytes. We have found increased in vitro MGAT activity during adipocyte differentiation, but most of this MGAT activity come from DGAT1. Also, DGAT1 may try to compensate for the absence of MGAT1 in adipocytes by increasing both MGAT and DGAT activity. This result suggests a post-translational modification of DGAT1 in adipocytes since the mRNA expression level of DGAT1 did not change during adipocyte differentiation. MGAT1 may have a role in triacylglycerol synthesis and storage in lipid droplets since the size of lipid droplets and the synthesis of triacylglycerol was decreased in the absence of MGAT1. The function of MGAT2 in adipocytes is not clear but may have a role in upregulating DGAT1 activity in the absence of MGAT1. However, the differentiation of adipocytes does not depend on either MGAT enzyme. We also tried to explore the role of MGAT1 and MGAT2 in lipolysis in adipocytes but due to a technical problem, we could not conclude anything from this lipolytic experiment.
In summary, this study suggests the role of monoacylglycerol pathway in regulating triacylglycerol metabolism in adipocytes.
Description
Keywords
adipose tissue, monoacylglycerol acyltransferase
Citation
Degree
Master of Science (M.Sc.)
Department
Biochemistry
Program
Biochemistry