@article{9f4d9ea003ee48c1bd153c2195b741e3,
title = "Hepatic monoacylglycerol acyltransferase 1 is induced by prolonged food deprivation to modulate the hepatic fasting response",
abstract = "During prolonged fasting, the liver plays a central role in maintaining systemic energy homeostasis by producing glucose and ketones in processes fueled by oxidation of fatty acids liberated from adipose tissue. In mice, this is accompanied by transient hepatic accumulation of glycerolipids. We found that the hepatic expression of monoacylglycerol acyltransferase 1 (Mogat1), an enzyme with monoacylglycerol acyltransferase (MGAT) activity that produces diacylglycerol from monoacylglycerol, was significantly increased in the liver of fasted mice compared with mice given ad libitum access to food. Basal and fastinginduced expression of Mogat1 was markedly diminished in the liver of mice lacking the transcription factor PPAR. Suppressing Mogat1 expression in liver and adipose tissue with antisense oligonucleotides (ASOs) reduced hepatic MGAT activity and triglyceride content compared with fasted controls. Surprisingly, the expression of many other PPAR target genes and PPAR activity was also decreased in mice given Mogat1 ASOs. When mice treated with control or Mogat1 ASOs were gavaged with the PPAR ligand, WY14643, and then fasted for 18 h, WY14643 administration reversed the effects of Mogat1 ASOs on PPAR target gene expression and liver triglyceride content. In conclusion, Mogat1 is a fastinginduced PPAR target gene that may feed forward to regulate liver PPAR activity during food deprivation.",
keywords = "Fasting, Fatty acid/oxidation, Lipidomics, Liver, MGAT, Mogat1, PPARs, Triglycerides",
author = "Lutkewitte, {Andrew J.} and McCommis, {Kyle S.} and Schweitzer, {George G.} and Chambers, {Kari T.} and Graham, {Mark J.} and Lingjue Wang and Patti, {Gary J.} and Hall, {Angela M.} and Finck, {Brian N.}",
note = "Funding Information: This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants T32 DK07120 (A.J.L., training grant), P30 DK052574 (K.S.M.), R56 DK111735 (A.M.H.), and R01 DK078187 (B.N.F); National Heart, Lung, and Blood Institute Grant K99 HL136658 (K.S.M.); and American Diabetes Association Grant 1-17-IBS-109 (A.M.H.). The Core services of the Diabetes Research Center (P30 DK020579) and the Nutrition Obesity Research Center (P30 DK56341) at the Washington University School of Medicine also supported this work. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants T32 DK07120 (A.J.L., training grant), P30 DK052574 (K.S.M.), R56 DK111735 (A.M.H.), and R01 DK078187 (B.N.F); National Heart, Lung, and Blood Institute Grant K99 HL136658 (K.S.M.); and American Diabetes Association Grant 1-17-IBS-109 (A.M.H.). The Core services of the Diabetes Research Center (P30 DK020579) and the Nutrition Obesity Research Center (P30 DK56341) at the Washington University School of Medicine also supported this work. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Manuscript received 4 September 2018 and in revised form 5 December 2018. Published, JLR Papers in Press, January 4, 2019 DOI https://doi.org/10.1194/jlr.M089722 Publisher Copyright: Copyright {\textcopyright} 2019 Lutkewitte et al.",
year = "2019",
doi = "10.1194/jlr.M089722",
language = "English",
volume = "60",
pages = "528--538",
journal = "Journal of Lipid Research",
issn = "0022-2275",
number = "3",
}