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

Tobita, T and Guzman-Lepe, J and Takeishi, K and Nakao, T and Wang, Y and Meng, F and Deng, CX and De L'Hortet, AC and Soto-Gutierrez, A (2016) SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids. PLoS ONE, 11 (2).

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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.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tobita, T
Guzman-Lepe, J
Takeishi, Kkat106@pitt.eduKAT106
Nakao, Tnakaot@pitt.eduNAKAOT
Wang, Y
Meng, F
Deng, CX
De L'Hortet, AC
Soto-Gutierrez, A
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorGuillou, HervéUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 February 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0149344
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Date Deposited: 23 Aug 2016 15:07
Last Modified: 02 Apr 2021 19:55
URI: http://d-scholarship.pitt.edu/id/eprint/28305

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