Longitudinal study of tissue- and subunit-specific obesity-induced regulation of the pyruvate dehydrogenase complex
Abstract
The tissue-specific expression of the mitochondrial pyruvate dehydrogenase complex (PDHc) has been studied in an animal model of obesity with hyperinsulinemia, the obese (fa/fa) Zucker rat. Liver and heart were obtained from 4 and 8 week-old obese rats and age-matched lean animals, and in each tissue the following parameters were analyzed: (1) total activity of the mitochondrial PDHc; (2) abundance of the mitochondrial PDHc subunits on Western blots; and (3) abundance of the E1alpha and E1beta subunit mRNAs on Northern blots and semi-quantitative RT-PCR. Regardless of age, obese rats showed an increase in liver total PDHc activity and a coordinate increase in liver E1alpha and E1beta PDHc subunit abundance. At 4 weeks, obese rats also showed an increase in liver PDH E1alpha mRNA level, but regardless of age E1beta mRNA level was unchanged. In contrast, neither total PDHc activity nor the concentration of its protein subunits were increased in heart of obese rats. Thus, obese Zucker rats display a liver-specific early increase in PDHc which results from a selective up-regulation of the E1alpha gene expression.
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Although deficient muscle substrate oxidation capacity is observed during obesity, there is no alteration in mitochondrial activities of pivotal enzymes such as citrate synthase, succinate dehydrogenase, or β-hydroxyacetyl-CoA dehydrogenase.
“However, and although deficient muscle substrate oxidation capacity is observed during obesity, there is no alteration in mitochondrial activities of pivotal enzymes such as citrate synthase, succinate dehydrogenase, or -hydroxyacetyl-CoA dehydrogenase (19 -21).”
From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [21]
The mechanisms by which obesity leads to deficient muscle substrate oxidation remain unexplained and are concomitant with unaltered mitochondrial activities of pivotal enzymes such as pyruvate dehydrogenase, citrate synthase, succinate dehydrogenase, or beta-hydroxyacetyl-CoA dehydrogenase.
“In particular, the mechanisms by which obesity leads to a deficient muscle substrate oxidation remain unexplained and are concomitant with unaltered mitochondrial activities of pivotal enzymes such as pyruvate dehydrogenase, citrate synthase, succinate dehydrogenase, or औ-hydroxyacetyl-CoA dehydrogenase (44-46”
From Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism (2003) · cites this paper as [46]
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Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism
Bach, D., Pich, S., Soriano, F. X., Vega, N., Baumgartner, B., Oriola, J., Daugaard, J. R., Lloberas, J., Camps, M., Zierath, J. R., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212754200 · Cited by 832 · see citing works
Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle
Bach, D., Naon, D., Pich, S., Soriano, F. X., Vega, N., Rieusset, J., Laville, M., Guillet, C., Boirie, Y., Wallberg-Henriksson, H., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2685 · Cited by 369 · see citing works
- Authors
- Amessou, M., Fouque, F., Soussi, N., Desbuquois, B., Hainaut, I., Girard, J., & Benelli, C.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Amessou, Mohamed
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 1998-09
- Volume
- 144
- Issue
- 1-2
- Pages
- 139-147
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W1980523626
- Cited by
- 8
- References
- 47
- FWCI
- 0.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- pyruvate dehydrogenase complex, obesity, hyperinsulinemia, Zucker fatty rats, gene expression regulation, liver, heart, mitochondrial enzyme activity, tissue-specific gene regulation
- MeSH terms
- Animals, Hyperinsulinism, Longitudinal Studies, Mitochondria, Heart, Mitochondria, Liver, Obesity, Organ Specificity, Pyruvate Dehydrogenase Complex, Rats, Zucker, Blotting, Northern, Blotting, Western, Up-Regulation, Gene Expression Regulation, Enzymologic, Matched-Pair Analysis, Reverse Transcriptase Polymerase Chain Reaction, Pyruvate Dehydrogenase (Lipoamide), Rats
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