Hepatic monoacylglycerol acyltransferase 1 is induced by prolonged food deprivation to modulate the hepatic fasting response

Andrew J. Lutkewitte, Kyle S. McCommis, George G. Schweitzer, Kari T. Chambers, Mark J. Graham, Lingjue Wang, Gary J. Patti, Angela M. Hall, Brian N. Finck

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1 Scopus citations

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.

Original languageEnglish
Pages (from-to)528-538
Number of pages11
JournalJournal of lipid research
Volume60
Issue number3
DOIs
StatePublished - Jan 1 2019

Keywords

  • Fasting
  • Fatty acid/oxidation
  • Lipidomics
  • Liver
  • MGAT
  • Mogat1
  • PPARs
  • Triglycerides

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    Lutkewitte, A. J., McCommis, K. S., Schweitzer, G. G., Chambers, K. T., Graham, M. J., Wang, L., Patti, G. J., Hall, A. M., & Finck, B. N. (2019). Hepatic monoacylglycerol acyltransferase 1 is induced by prolonged food deprivation to modulate the hepatic fasting response. Journal of lipid research, 60(3), 528-538. https://doi.org/10.1194/jlr.M089722