ArticleThe Biochemical journal2002
Peroxisome-proliferator-activated receptor-alpha (PPARalpha) deficiency leads to dysregulation of hepatic lipid and carbohydrate metabolism by fatty acids and insulin.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 159 citations in OpenAlex.
- Loss ofCells · 2026Article
- Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.Clinical science (London, England : 1979) · 2025Review
- Dietary sanguinarine supplementation recovers the decrease in muscle quality and nutrient composition induced by high-fat diets of grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Characteristics of glucose and lipid metabolism and the interaction between gut microbiota and colonic mucosal immunity in pigs during cold exposure.Journal of animal science and biotechnology · 2023Article
- Effects of Different Dietary Starch Sources and Digestible Lysine Levels on Carcass Traits, Serum Metabolites, Liver Lipid and Breast Muscle Protein Metabolism in Broiler Chickens.Animals : an open access journal from MDPI · 2023Article
- Indole alkaloids of Alstonia scholaris (L.) R. Br. alleviated nonalcoholic fatty liver disease in mice fed with high-fat diet.Natural products and bioprospecting · 2022Article
- Effects of peroxisome proliferator activated receptor-α agonist on growth performance, blood profiles, gene expression related to liver fat metabolism in broilers fed diets containing corn naturally contaminated with mycotoxins.Frontiers in veterinary science · 2022Article
- Comparative Transcriptome Analysis Reveals the Mechanism Associated With Dynamic Changes in Meat Quality of the Longissimus Thoracis Muscle in Tibetan Sheep at Different Growth Stages.Frontiers in veterinary science · 2022Article
- The transcription factors CREBH, PPARa, and FOXO1 as critical hepatic mediators of diet-induced metabolic dysregulation.The Journal of nutritional biochemistry · 2021Review
- Hepatic metabolic regulation by nuclear factor E4BP4.Journal of molecular endocrinology · 2021Review
- Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm.Nutrients · 2020Review
- Review
- Low Expression of Sirtuin 1 in the Dairy Cows with Mild Fatty Liver Alters Hepatic Lipid Metabolism.Animals : an open access journal from MDPI · 2020Article
- Transcript profile of skeletal muscle lipid metabolism genes affected by diet in a piglet model of low birth weight.PloS one · 2019Article
- Hexane-Isopropanolic Extract of Tungrymbai, a North-East Indian fermented soybean food prevents hepatic steatosis via regulating AMPK-mediated SREBP/FAS/ACC/HMGCR and PPARα/CPT1A/UCP2 pathways.Scientific reports · 2018Article
- Human germline hedgehog pathway mutations predispose to fatty liver.Journal of hepatology · 2017Article
- MUC2 mucin deficiency alters inflammatory and metabolic pathways in the mouse intestinal mucosa.Oncotarget · 2017Article
- Zinc finger protein 407 overexpression upregulates PPAR target gene expression and improves glucose homeostasis in mice.American journal of physiology. Endocrinology and metabolism · 2016Article
- Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans.International journal of molecular sciences · 2016Review
- PPARα (Peroxisome Proliferator-activated Receptor α) Activation Reduces Hepatic CEACAM1 Protein Expression to Regulate Fatty Acid Oxidation during Fasting-refeeding Transition.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of the present study was to determine whether peroxisome-proliferator-activated receptor-alpha (PPARalpha) deficiency disrupts the normal regulation of triacylglycerol (TAG) accumulation, hepatic lipogenesis and glycogenesis by fatty acids and insulin using PPARalpha-null mice. In wild-type mice, hepatic TAG concentrations increased (P<0.01) with fasting (24 h), with substantial reversal after refeeding (6 h). Hepatic TAG levels in fed PPARalpha-null mice were 2.4-fold higher than in the wild-type (P<0.05), increased with fasting, but remained elevated after refeeding. PPARalpha deficiency also impaired hepatic glycogen repletion (P<0.001), despite normal insulin and glucose levels after refeeding. Higher levels of plasma insulin were required to support similar levels of hepatic lipogenesis de novo ((3)H(2)O incorporation) in the PPARalpha-null mice compared with the wild-type. This difference was reflected by corresponding changes in the relationship between plasma insulin and the mRNA expression of the lipogenic transcription factor sterol-regulatory-element-binding protein-1c, and that of one of its known targets, fatty acid synthase. In wild-type mice, hepatic pyruvate dehydrogenase kinase (PDK) 4 protein expression (a downstream marker of altered fatty acid catabolism) increased (P<0.01) in response to fasting, with suppression (P<0.001) by refeeding. Although PDK4 up-regulation after fasting was halved by PPARalpha deficiency, PDK4 suppression after refeeding was attenuated. In summary, PPARalpha deficiency leads to accumulation of hepatic TAG and elicits dysregulation of hepatic lipid and carbohydrate metabolism, emphasizing the importance of precise control of lipid oxidation for hepatic fuel homoeostasis.
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