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Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice

The liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids via de novo lipogenesis (DNL) when carbohydrates are abundant. Mitochondrial pyruvate metabolism is thought to play important roles in...

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Autores principales: Yiew, Nicole K.H., Deja, Stanislaw, Ferguson, Daniel, Cho, Kevin, Jarasvaraparn, Chaowapong, Jacome-Sosa, Miriam, Lutkewitte, Andrew J., Mukherjee, Sandip, Fu, Xiaorong, Singer, Jason M., Patti, Gary J., Burgess, Shawn C., Finck, Brian N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949129/
https://www.ncbi.nlm.nih.gov/pubmed/36824879
http://dx.doi.org/10.1101/2023.02.17.528992
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author Yiew, Nicole K.H.
Deja, Stanislaw
Ferguson, Daniel
Cho, Kevin
Jarasvaraparn, Chaowapong
Jacome-Sosa, Miriam
Lutkewitte, Andrew J.
Mukherjee, Sandip
Fu, Xiaorong
Singer, Jason M.
Patti, Gary J.
Burgess, Shawn C.
Finck, Brian N.
author_facet Yiew, Nicole K.H.
Deja, Stanislaw
Ferguson, Daniel
Cho, Kevin
Jarasvaraparn, Chaowapong
Jacome-Sosa, Miriam
Lutkewitte, Andrew J.
Mukherjee, Sandip
Fu, Xiaorong
Singer, Jason M.
Patti, Gary J.
Burgess, Shawn C.
Finck, Brian N.
author_sort Yiew, Nicole K.H.
collection PubMed
description The liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids via de novo lipogenesis (DNL) when carbohydrates are abundant. Mitochondrial pyruvate metabolism is thought to play important roles in both gluconeogenesis and DNL. We examined the effects of hepatocyte-specific mitochondrial pyruvate carrier (MPC) deletion on the fasting-refeeding response. Rates of DNL during refeeding were impaired by liver MPC deletion, but this did not reduce intrahepatic lipid content. During fasting, glycerol is converted to glucose by two pathways; a direct cytosolic pathway essentially reversing glycolysis and an indirect mitochondrial pathway requiring the MPC. MPC deletion reduced the incorporation of (13)C-glycerol into TCA cycle metabolites but not into newly synthesized glucose. However, suppression of glycerol metabolism did not affect glucose concentrations in fasted hepatocyte-specific MPC-deficient mice. Thus, glucose production by kidney and intestine may compensate for MPC deficiency in hepatocytes.
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spelling pubmed-99491292023-02-24 Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice Yiew, Nicole K.H. Deja, Stanislaw Ferguson, Daniel Cho, Kevin Jarasvaraparn, Chaowapong Jacome-Sosa, Miriam Lutkewitte, Andrew J. Mukherjee, Sandip Fu, Xiaorong Singer, Jason M. Patti, Gary J. Burgess, Shawn C. Finck, Brian N. bioRxiv Article The liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids via de novo lipogenesis (DNL) when carbohydrates are abundant. Mitochondrial pyruvate metabolism is thought to play important roles in both gluconeogenesis and DNL. We examined the effects of hepatocyte-specific mitochondrial pyruvate carrier (MPC) deletion on the fasting-refeeding response. Rates of DNL during refeeding were impaired by liver MPC deletion, but this did not reduce intrahepatic lipid content. During fasting, glycerol is converted to glucose by two pathways; a direct cytosolic pathway essentially reversing glycolysis and an indirect mitochondrial pathway requiring the MPC. MPC deletion reduced the incorporation of (13)C-glycerol into TCA cycle metabolites but not into newly synthesized glucose. However, suppression of glycerol metabolism did not affect glucose concentrations in fasted hepatocyte-specific MPC-deficient mice. Thus, glucose production by kidney and intestine may compensate for MPC deficiency in hepatocytes. Cold Spring Harbor Laboratory 2023-08-24 /pmc/articles/PMC9949129/ /pubmed/36824879 http://dx.doi.org/10.1101/2023.02.17.528992 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Yiew, Nicole K.H.
Deja, Stanislaw
Ferguson, Daniel
Cho, Kevin
Jarasvaraparn, Chaowapong
Jacome-Sosa, Miriam
Lutkewitte, Andrew J.
Mukherjee, Sandip
Fu, Xiaorong
Singer, Jason M.
Patti, Gary J.
Burgess, Shawn C.
Finck, Brian N.
Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
title Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
title_full Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
title_fullStr Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
title_full_unstemmed Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
title_short Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
title_sort effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949129/
https://www.ncbi.nlm.nih.gov/pubmed/36824879
http://dx.doi.org/10.1101/2023.02.17.528992
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