Hepatic rRNA transcription regulates high-fat-diet-induced obesity

Cell Rep. 2014 May 8;7(3):807-20. doi: 10.1016/j.celrep.2014.03.038. Epub 2014 Apr 18.


Ribosome biosynthesis is a major intracellular energy-consuming process. We previously identified a nucleolar factor, nucleomethylin (NML), which regulates intracellular energy consumption by limiting rRNA transcription. Here, we show that, in livers of obese mice, the recruitment of NML to rRNA gene loci is increased to repress rRNA transcription. To clarify the relationship between obesity and rRNA transcription, we generated NML-null (NML-KO) mice. NML-KO mice show elevated rRNA level, reduced ATP concentration, and reduced lipid accumulation in the liver. Furthermore, in high-fat-diet (HFD)-fed NML-KO mice, hepatic rRNA levels are not decreased. Both weight gain and fat accumulation in HFD-fed NML-KO mice are significantly lower than those in HFD-fed wild-type mice. These findings indicate that rRNA transcriptional activation promotes hepatic energy consumption, which alters hepatic lipid metabolism. Namely, hepatic rRNA transcriptional repression by HFD feeding is essential for energy storage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Diet, High-Fat*
  • Energy Metabolism
  • Fatty Acids / biosynthesis
  • Gene Expression
  • Lipid Metabolism / genetics
  • Liver / diagnostic imaging
  • Liver / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Obese
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism*
  • Sirtuin 1 / metabolism
  • Tomography, X-Ray Computed
  • Transcription, Genetic


  • Fatty Acids
  • Nuclear Proteins
  • RNA, Ribosomal
  • Adenosine Triphosphate
  • Sirt1 protein, mouse
  • Sirtuin 1

Associated data

  • GEO/GSE48191