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bioRxiv · 10.1101/2022.02.14.480414

Monoacylglycerol O-acyltransferase 1 is required for adipocyte differentiation in vitro but does not affect adiposity in mice

Singer, J. M.·Shew, T. M.·Ferguson, D.·Renkemeyer, M. K.·Pietka, T. A.·Hall, A. M.·Finck, B. N.·Lutkewitte, A. J.
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Abstract

ObjectiveMonoacylglycerol O-acyltransferase 1 (Mogat1), a lipogenic enzyme that converts monoacylglycerol to diacylglycerol, is highly expressed in adipocytes and may regulate lipolysis by re-esterifying fatty acids released during times when lipolytic rates are low. However, the role of Mogat1 in regulating adipocyte fat storage during differentiation and diet-induced obesity is relatively understudied. MethodsHere we generated adipocyte-specific Mogat1 knockout mice and subjected them to a high-fat diet to determine the effects of Mogat1 deficiency on diet-induced obesity. We also used Mogat1 floxed mice to develop preadipocyte cell lines wherein Mogat1 could be conditionally knocked out to study adipocyte differentiation in vitro. ResultsIn preadipocytes, we found that Mogat1 knockout at the onset of preadipocyte differentiation prevented the accumulation of glycerolipids and reduced the differentiation capacity of preadipocytes. However, the loss of adipocyte Mogat1 did not affect weight gain or fat mass induced by high-fat diet in mice. Furthermore, loss of Mogat1 in adipocytes did not affect plasma lipid or glucose concentrations or insulin tolerance. ConclusionsThese data suggest Mogat1 may play a role in adipocyte differentiation in vitro but not adipose tissue expansion in response to nutrient overload in mice. STUDY IMPORTANCEO_ST_ABSWhat is already known?C_ST_ABSO_LIAdipose tissue expansion through adipocyte precursor cell differentiation is critical for proper lipid storage during nutrient overload. C_LIO_LIMonoacylglycerol O-acyltransferase 1 (Mogat1), a lipogenic enzyme, is highly induced during adipocyte differentiation of human and mouse precursor cells and is reduced in patients with obesity and metabolic dysfunction. C_LI What does this study add?O_LIMogat1 deletion during early adipocyte differentiation reduces differentiation capacity, adipogenic gene expression and lowers glycerolipid content of differentiated adipocytes. C_LIO_LIAdipocyte Mogat1 expression is dispensable for adiposity and metabolic outcomes high-fat fed mice and suggests compensation from other glycerolipid synthesis enzymes. C_LI How might these results change the direction of research?O_LIUnderstanding the molecular mechanisms of glycerolipid metabolism healthy adipose tissue expansion. C_LI

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Singer, J. M., Shew, T. M., Ferguson, D., Renkemeyer, M. K., Pietka, T. A., Hall, A. M., Finck, B. N., Lutkewitte, A. J.. 2022-02-15. Monoacylglycerol O-acyltransferase 1 is required for adipocyte differentiation in vitro but does not affect adiposity in mice. https://doi.org/10.1101/2022.02.14.480414

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