The Experts below are selected from a list of 16785 Experts worldwide ranked by ideXlab platform
Craig R. Malloy - One of the best experts on this subject based on the ideXlab platform.
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an oral load of 13c3 glycerol and blood nmr analysis detect fatty Acid esterification pentose phosphate pathway and glycerol metabolism through the Tricarboxylic Acid Cycle in human liver
Journal of Biological Chemistry, 2016Co-Authors: Eunsook S Jin, Dean A Sherry, Craig R. MalloyAbstract:Drugs and other interventions for high impact hepatic diseases often target biochemical pathways such as gluconeogenesis, lipogenesis, or the metabolic response to oxidative stress. However, traditional liver function tests do not provide quantitative data about these pathways. In this study, we developed a simple method to evaluate these processes by NMR analysis of plasma metabolites. Healthy subjects ingested [U-(13)C3]glycerol, and blood was drawn at multiple times. Each subject completed three visits under differing nutritional states. High resolution (13)C NMR spectra of plasma triacylglycerols and glucose provided new insights into a number of hepatic processes including fatty Acid esterification, the pentose phosphate pathway, and gluconeogenesis through the Tricarboxylic Acid Cycle. Fasting stimulated pentose phosphate pathway activity and metabolism of [U-(13)C3]glycerol in the Tricarboxylic Acid Cycle prior to gluconeogenesis or glyceroneogenesis. Fatty Acid esterification was transient in the fasted state but continuous under fed conditions. We conclude that a simple NMR analysis of blood metabolites provides an important biomarker of pentose phosphate pathway activity, triacylglycerol synthesis, and flux through anaplerotic pathways in mitochondria of human liver.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:The peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1alpha deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1alpha(-/-) mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1alpha(-/-) livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1alpha target genes involved in gluconeogenesis was unaltered in PGC-1alpha(-/-) compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid beta-oxidation pathways was also diminished in PGC-1alpha(-/-) livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1alpha(-/-) mice and was activated by PGC-1alpha overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1alpha deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid beta-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:Abstract The peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1α deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1α–/– mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1α–/– livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1α target genes involved in gluconeogenesis was unaltered in PGC-1α–/– compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid β-oxidation pathways was also diminished in PGC-1α–/– livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1α–/– mice and was activated by PGC-1α overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1α deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid β-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
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Is there tight channelling in the Tricarboxylic Acid Cycle metabolon
Biochemical Society transactions, 1991Co-Authors: Balazs Sumegi, A D Sherry, Craig R. Malloy, C. Evans, Paul A. SrereAbstract:Is there tight channelling in the Tricarboxylic Acid Cycle metabolon? Balazs Sumegi,§ A. Dean Sherry,§ Craig R. Malloy,*$ Claudia Evans*t and Paul A. Srere*t *Pre-Clinical Science Unit of the Department of Veterans Affairs Medical Center, tDepartment of Biochemistry and $The Mary Nell & Ralph B. Rogers N.M.R. Center, The University of Texas Southwestern Medical Center at Dallas, 4500 South Lancaster Road, Dallas, TX 752 16, U.S.A. and §Chemistry Department, The University of Texas at Dallas, Richardson, TX 75083-0688, U.S.A.
Brian N Finck - One of the best experts on this subject based on the ideXlab platform.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:The peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1alpha deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1alpha(-/-) mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1alpha(-/-) livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1alpha target genes involved in gluconeogenesis was unaltered in PGC-1alpha(-/-) compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid beta-oxidation pathways was also diminished in PGC-1alpha(-/-) livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1alpha(-/-) mice and was activated by PGC-1alpha overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1alpha deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid beta-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:Abstract The peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1α deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1α–/– mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1α–/– livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1α target genes involved in gluconeogenesis was unaltered in PGC-1α–/– compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid β-oxidation pathways was also diminished in PGC-1α–/– livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1α–/– mice and was activated by PGC-1α overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1α deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid β-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
Dean A Sherry - One of the best experts on this subject based on the ideXlab platform.
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an oral load of 13c3 glycerol and blood nmr analysis detect fatty Acid esterification pentose phosphate pathway and glycerol metabolism through the Tricarboxylic Acid Cycle in human liver
Journal of Biological Chemistry, 2016Co-Authors: Eunsook S Jin, Dean A Sherry, Craig R. MalloyAbstract:Drugs and other interventions for high impact hepatic diseases often target biochemical pathways such as gluconeogenesis, lipogenesis, or the metabolic response to oxidative stress. However, traditional liver function tests do not provide quantitative data about these pathways. In this study, we developed a simple method to evaluate these processes by NMR analysis of plasma metabolites. Healthy subjects ingested [U-(13)C3]glycerol, and blood was drawn at multiple times. Each subject completed three visits under differing nutritional states. High resolution (13)C NMR spectra of plasma triacylglycerols and glucose provided new insights into a number of hepatic processes including fatty Acid esterification, the pentose phosphate pathway, and gluconeogenesis through the Tricarboxylic Acid Cycle. Fasting stimulated pentose phosphate pathway activity and metabolism of [U-(13)C3]glycerol in the Tricarboxylic Acid Cycle prior to gluconeogenesis or glyceroneogenesis. Fatty Acid esterification was transient in the fasted state but continuous under fed conditions. We conclude that a simple NMR analysis of blood metabolites provides an important biomarker of pentose phosphate pathway activity, triacylglycerol synthesis, and flux through anaplerotic pathways in mitochondria of human liver.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:The peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1alpha deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1alpha(-/-) mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1alpha(-/-) livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1alpha target genes involved in gluconeogenesis was unaltered in PGC-1alpha(-/-) compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid beta-oxidation pathways was also diminished in PGC-1alpha(-/-) livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1alpha(-/-) mice and was activated by PGC-1alpha overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1alpha deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid beta-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:Abstract The peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1α deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1α–/– mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1α–/– livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1α target genes involved in gluconeogenesis was unaltered in PGC-1α–/– compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid β-oxidation pathways was also diminished in PGC-1α–/– livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1α–/– mice and was activated by PGC-1α overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1α deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid β-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
Shawn C Burgess - One of the best experts on this subject based on the ideXlab platform.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:The peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1alpha deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1alpha(-/-) mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1alpha(-/-) livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1alpha target genes involved in gluconeogenesis was unaltered in PGC-1alpha(-/-) compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid beta-oxidation pathways was also diminished in PGC-1alpha(-/-) livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1alpha(-/-) mice and was activated by PGC-1alpha overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1alpha deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid beta-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:Abstract The peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1α deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1α–/– mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1α–/– livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1α target genes involved in gluconeogenesis was unaltered in PGC-1α–/– compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid β-oxidation pathways was also diminished in PGC-1α–/– livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1α–/– mice and was activated by PGC-1α overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1α deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid β-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
Teresa C Leone - One of the best experts on this subject based on the ideXlab platform.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:The peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1alpha deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1alpha(-/-) mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1alpha(-/-) livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1alpha target genes involved in gluconeogenesis was unaltered in PGC-1alpha(-/-) compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid beta-oxidation pathways was also diminished in PGC-1alpha(-/-) livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1alpha(-/-) mice and was activated by PGC-1alpha overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1alpha deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid beta-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
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diminished hepatic gluconeogenesis via defects in Tricarboxylic Acid Cycle flux in peroxisome proliferator activated receptor γ coactivator 1α pgc 1α deficient mice
Journal of Biological Chemistry, 2006Co-Authors: Shawn C Burgess, Craig R. Malloy, Teresa C Leone, Adam R Wende, Michelle A Croce, Zhouji Chen, Dean A Sherry, Brian N FinckAbstract:Abstract The peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) is a highly inducible transcriptional coactivator implicated in the coordinate regulation of genes encoding enzymes involved in hepatic fatty Acid oxidation, oxidative phosphorylation, and gluconeogenesis. The present study sought to assess the effects of chronic PGC-1α deficiency on metabolic flux through the hepatic gluconeogenic, fatty Acid oxidation, and Tricarboxylic Acid Cycle pathways. To this end, hepatic metabolism was assessed in wild-type (WT) and PGC-1α–/– mice using isotopomer-based NMR with complementary gene expression analyses. Hepatic glucose production was diminished in PGC-1α–/– livers coincident with reduced gluconeogenic flux from phosphoenolpyruvate. Surprisingly, the expression of PGC-1α target genes involved in gluconeogenesis was unaltered in PGC-1α–/– compared with WT mice under fed and fasted conditions. Flux through Tricarboxylic Acid Cycle and mitochondrial fatty Acid β-oxidation pathways was also diminished in PGC-1α–/– livers. The expression of multiple genes encoding Tricarboxylic Acid Cycle and oxidative phosphorylation enzymes was significantly depressed in PGC-1α–/– mice and was activated by PGC-1α overexpression in the livers of WT mice. Collectively, these findings suggest that chronic whole-animal PGC-1α deficiency results in defects in hepatic glucose production that are secondary to diminished fatty Acid β-oxidation and Tricarboxylic Acid Cycle flux rather than abnormalities in gluconeogenic enzyme gene expression per se.
