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SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase
Calorie restriction abates aging and cardiometabolic disease by activating metabolic signaling pathways, including nicotinamide adenine dinucleotide (NAD(+)) biosynthesis and salvage. Nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting in NAD(+) salvage, yet hepatocyte NAMPT actions duri...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885655/ https://www.ncbi.nlm.nih.gov/pubmed/35228549 http://dx.doi.org/10.1038/s41467-022-28717-7 |
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author | Higgins, Cassandra B. Mayer, Allyson L. Zhang, Yiming Franczyk, Michael Ballentine, Samuel Yoshino, Jun DeBosch, Brian J. |
author_facet | Higgins, Cassandra B. Mayer, Allyson L. Zhang, Yiming Franczyk, Michael Ballentine, Samuel Yoshino, Jun DeBosch, Brian J. |
author_sort | Higgins, Cassandra B. |
collection | PubMed |
description | Calorie restriction abates aging and cardiometabolic disease by activating metabolic signaling pathways, including nicotinamide adenine dinucleotide (NAD(+)) biosynthesis and salvage. Nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting in NAD(+) salvage, yet hepatocyte NAMPT actions during fasting and metabolic duress remain unclear. We demonstrate that hepatocyte NAMPT is upregulated in fasting mice, and in isolated hepatocytes subjected to nutrient withdrawal. Mice lacking hepatocyte NAMPT exhibit defective FGF21 activation and thermal regulation during fasting, and are sensitized to diet-induced glucose intolerance. Hepatocyte NAMPT overexpression induced FGF21 and adipose browning, improved glucose homeostasis, and attenuated dyslipidemia in obese mice. Hepatocyte SIRT1 deletion reversed hepatocyte NAMPT effects on dark-cycle thermogenesis, and hepatic FGF21 expression, but SIRT1 was dispensable for NAMPT insulin-sensitizing, anti-dyslipidemic, and light-cycle thermogenic effects. Hepatocyte NAMPT thus conveys key aspects of the fasting response, which selectively dissociate through hepatocyte SIRT1. Modulating hepatocyte NAD(+) is thus a potential mechanism through which to attenuate fasting-responsive disease. |
format | Online Article Text |
id | pubmed-8885655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88856552022-03-17 SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase Higgins, Cassandra B. Mayer, Allyson L. Zhang, Yiming Franczyk, Michael Ballentine, Samuel Yoshino, Jun DeBosch, Brian J. Nat Commun Article Calorie restriction abates aging and cardiometabolic disease by activating metabolic signaling pathways, including nicotinamide adenine dinucleotide (NAD(+)) biosynthesis and salvage. Nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting in NAD(+) salvage, yet hepatocyte NAMPT actions during fasting and metabolic duress remain unclear. We demonstrate that hepatocyte NAMPT is upregulated in fasting mice, and in isolated hepatocytes subjected to nutrient withdrawal. Mice lacking hepatocyte NAMPT exhibit defective FGF21 activation and thermal regulation during fasting, and are sensitized to diet-induced glucose intolerance. Hepatocyte NAMPT overexpression induced FGF21 and adipose browning, improved glucose homeostasis, and attenuated dyslipidemia in obese mice. Hepatocyte SIRT1 deletion reversed hepatocyte NAMPT effects on dark-cycle thermogenesis, and hepatic FGF21 expression, but SIRT1 was dispensable for NAMPT insulin-sensitizing, anti-dyslipidemic, and light-cycle thermogenic effects. Hepatocyte NAMPT thus conveys key aspects of the fasting response, which selectively dissociate through hepatocyte SIRT1. Modulating hepatocyte NAD(+) is thus a potential mechanism through which to attenuate fasting-responsive disease. Nature Publishing Group UK 2022-02-28 /pmc/articles/PMC8885655/ /pubmed/35228549 http://dx.doi.org/10.1038/s41467-022-28717-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Higgins, Cassandra B. Mayer, Allyson L. Zhang, Yiming Franczyk, Michael Ballentine, Samuel Yoshino, Jun DeBosch, Brian J. SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase |
title | SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase |
title_full | SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase |
title_fullStr | SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase |
title_full_unstemmed | SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase |
title_short | SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase |
title_sort | sirt1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885655/ https://www.ncbi.nlm.nih.gov/pubmed/35228549 http://dx.doi.org/10.1038/s41467-022-28717-7 |
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