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SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids
Tobita T.3; Guzman-Lepe J.3; Takeishi K.3; Nakao T.3; Wang Y.3; Meng F.3; Deng C.-X.5; De L'Hortet A.C.3; Soto-Gutierrez A.3
2016-02-01
Source PublicationPLoS ONE
ISSN1932-6203
Volume11Issue:2
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.

DOI10.1371/journal.pone.0149344
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000371221500038
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorDe L'Hortet A.C.; Soto-Gutierrez A.
Affiliation1.McGowan Institute for Regenerative Medicine
2.Peking University
3.University of Pittsburgh
4.University of Pittsburgh Medical Center
5.Universidade de Macau
Recommended Citation
GB/T 7714
Tobita T.,Guzman-Lepe J.,Takeishi K.,et al. SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids[J]. PLoS ONE,2016,11(2).
APA Tobita T..,Guzman-Lepe J..,Takeishi K..,Nakao T..,Wang Y..,...&Soto-Gutierrez A..(2016).SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids.PLoS ONE,11(2).
MLA Tobita T.,et al."SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids".PLoS ONE 11.2(2016).
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