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Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis

The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. W...

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Autores principales: Simcox, Judith A., Mitchell, Thomas Creighton, Gao, Yan, Just, Steven F., Cooksey, Robert, Cox, James, Ajioka, Richard, Jones, Deborah, Lee, Soh-hyun, King, Daniel, Huang, Jingyu, McClain, Donald A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375081/
https://www.ncbi.nlm.nih.gov/pubmed/25315005
http://dx.doi.org/10.2337/db14-0646
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author Simcox, Judith A.
Mitchell, Thomas Creighton
Gao, Yan
Just, Steven F.
Cooksey, Robert
Cox, James
Ajioka, Richard
Jones, Deborah
Lee, Soh-hyun
King, Daniel
Huang, Jingyu
McClain, Donald A.
author_facet Simcox, Judith A.
Mitchell, Thomas Creighton
Gao, Yan
Just, Steven F.
Cooksey, Robert
Cox, James
Ajioka, Richard
Jones, Deborah
Lee, Soh-hyun
King, Daniel
Huang, Jingyu
McClain, Donald A.
author_sort Simcox, Judith A.
collection PubMed
description The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling.
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spelling pubmed-43750812016-04-01 Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis Simcox, Judith A. Mitchell, Thomas Creighton Gao, Yan Just, Steven F. Cooksey, Robert Cox, James Ajioka, Richard Jones, Deborah Lee, Soh-hyun King, Daniel Huang, Jingyu McClain, Donald A. Diabetes Metabolism The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. American Diabetes Association 2015-04 2014-10-14 /pmc/articles/PMC4375081/ /pubmed/25315005 http://dx.doi.org/10.2337/db14-0646 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Metabolism
Simcox, Judith A.
Mitchell, Thomas Creighton
Gao, Yan
Just, Steven F.
Cooksey, Robert
Cox, James
Ajioka, Richard
Jones, Deborah
Lee, Soh-hyun
King, Daniel
Huang, Jingyu
McClain, Donald A.
Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis
title Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis
title_full Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis
title_fullStr Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis
title_full_unstemmed Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis
title_short Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis
title_sort dietary iron controls circadian hepatic glucose metabolism through heme synthesis
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375081/
https://www.ncbi.nlm.nih.gov/pubmed/25315005
http://dx.doi.org/10.2337/db14-0646
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