ArticleAmerican journal of physiology. Endocrinology and metabolism2016
Lack of mitochondria-generated acetyl-CoA by pyruvate dehydrogenase complex downregulates gene expression in the hepatic de novo lipogenic pathway.
Article in American journal of physiology. Endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Bisphosphoglycerate mutase is involved in glucose metabolism and progression of nonalcoholic fatty liver disease based on liver organoids.Human cell · 2026Article
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- The Stressogenic Impact of Bacterial Secretomes Is Modulated by the Size of the Milk Fat Globule Used as a Substrate.Foods (Basel, Switzerland) · 2024Article
- Article
- The Mitochondrial tRNAFrontiers in genetics · 2022Article
- Targeting hepatocyte carbohydrate transport to mimic fasting and calorie restriction.The FEBS journal · 2021Review
- Article
- Pyruvate Dehydrogenase as a Therapeutic Target for Nonalcoholic Fatty Liver Disease.ACS pharmacology & translational science · 2021Review
- Reprogramming of aerobic glycolysis in non-transformed mouse liver with pyruvate dehydrogenase complex deficiency.Physiological reports · 2021Article
- A Mitochondrial DNA Variant Elevates the Risk of Gallstone Disease by Altering Mitochondrial Function.Cellular and molecular gastroenterology and hepatology · 2021Article
- Drug discovery and treatment paradigms in nonalcoholic steatohepatitis.Endocrinology, diabetes & metabolism · 2020Review
- Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action.American journal of physiology. Endocrinology and metabolism · 2018Article
- Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism.Diabetes & metabolism journal · 2018Review
- Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation.Cancer research · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the absorptive state, the liver stores excess glucose as glycogen and synthesizes fatty acids for triglyceride synthesis for export as very low density lipoproteins. For de novo synthesis of fatty acids from glucose, the mitochondrial pyruvate dehydrogenase complex (PDC) is the gatekeeper for the generation of acetyl-CoA from glucose-derived pyruvate. Here, we tested the hypothesis that limiting the supply of PDC-generated acetyl-CoA from glucose would have an impact on expression of key genes in the lipogenic pathway. In the present study, although the postnatal growth of liver-specific PDC-deficient (L-PDCKO) male mice was largely unaltered, the mice developed hyperinsulinemia with lower blood glucose levels in the fed state. Serum and liver lipid triglyceride and cholesterol levels remained unaltered in L-PDCKO mice. Expression of several key genes (ACL, ACC1) in the lipogenic pathway and their upstream regulators (LXR, SREBP1, ChREBP) as well as several genes in glucose metabolism (Pklr, G6pd2, Pck1) and fatty acid oxidation (FAT, Cpt1a) was downregulated in livers from L-PDCKO mice. Interestingly, there was concomitant upregulation of lipogenic genes in adipose tissue from L-PDCKO mice. Although, the total hepatic acetyl-CoA content remained unaltered in L-PDCKO mice, modified acetylation profiles of proteins in the nuclear compartment suggested an important role for PDC-generated acetyl-CoA in gene expression in de novo fatty acid synthesis in the liver. This finding has important implications for the regulation of hepatic lipid synthesis in pathological states.
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