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SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet

Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely t...

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Autores principales: Nguyen, Long T., Mak, Crystal H., Chen, Hui, Zaky, Amgad A., Wong, Muh G., Pollock, Carol A., Saad, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356703/
https://www.ncbi.nlm.nih.gov/pubmed/30641941
http://dx.doi.org/10.3390/nu11010146
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author Nguyen, Long T.
Mak, Crystal H.
Chen, Hui
Zaky, Amgad A.
Wong, Muh G.
Pollock, Carol A.
Saad, Sonia
author_facet Nguyen, Long T.
Mak, Crystal H.
Chen, Hui
Zaky, Amgad A.
Wong, Muh G.
Pollock, Carol A.
Saad, Sonia
author_sort Nguyen, Long T.
collection PubMed
description Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury.
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spelling pubmed-63567032019-02-01 SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet Nguyen, Long T. Mak, Crystal H. Chen, Hui Zaky, Amgad A. Wong, Muh G. Pollock, Carol A. Saad, Sonia Nutrients Article Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury. MDPI 2019-01-11 /pmc/articles/PMC6356703/ /pubmed/30641941 http://dx.doi.org/10.3390/nu11010146 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nguyen, Long T.
Mak, Crystal H.
Chen, Hui
Zaky, Amgad A.
Wong, Muh G.
Pollock, Carol A.
Saad, Sonia
SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet
title SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet
title_full SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet
title_fullStr SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet
title_full_unstemmed SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet
title_short SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet
title_sort sirt1 attenuates kidney disorders in male offspring due to maternal high-fat diet
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356703/
https://www.ncbi.nlm.nih.gov/pubmed/30641941
http://dx.doi.org/10.3390/nu11010146
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