SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids

Takamasa Tobita, Jorge Guzman-Lepe, Kazuki Takeishi, Toshimasa Nakao, Yang Wang, Fanying Meng, Chu Xia Deng, Alexandra Collin De L'Hortet, Alejandro Soto-Gutierrez

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18 Citations (Scopus)

Abstract

There are unprecedented epidemics of obesity, such as type II diabetes and non-alcoholic fatty liver diseases (NAFLD) in developed countries. A concerning percentage of American children are being affected by obesity and NAFLD. Studies have suggested that the maternal environment in utero might play a role in the development of these diseases later in life. In this study, we documented that inhibiting SIRT1 signaling in human fetal hepatocytes rapidly led to an increase in intracellular glucose and lipids levels. More importantly, both de novo lipogenesis and gluconeogenesis related genes were upregulated upon SIRT1 inhibition. The AKT/FOXO1 pathway, a major negative regulator of gluconeogenesis, was decreased in the human fetal hepatocytes inhibited for SIRT1, consistent with the higher level of gluconeogenesis. These results indicate that SIRT1 is an important regulator of lipid and carbohydrate metabolisms within human fetal hepatocytes, acting as an adaptive transcriptional response to environmental changes.

Original languageEnglish
Article numbere0149344
JournalPloS one
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 2016
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Tobita, T., Guzman-Lepe, J., Takeishi, K., Nakao, T., Wang, Y., Meng, F., ... Soto-Gutierrez, A. (2016). SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids. PloS one, 11(2), [e0149344]. https://doi.org/10.1371/journal.pone.0149344