ArticleDiabetes2009
Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 151 citations in OpenAlex.
- Long-term multi-organ system abnormalities in mice exposed to antenatal and postnatal corticosteroids.Pediatric research · 2026Article
- Copper and hepatic lipid dysregulation: Mechanisms and implications.World journal of hepatology · 2025Review
- Reduced liver mitochondrial energy metabolism impairs food intake regulation following gastric preloads and fasting.Molecular metabolism · 2025Article
- Role of PGC-1α in the proliferation and metastasis of malignant tumors.Journal of molecular histology · 2025Review
- High-fat diet promotes prostate cancer metastasis via RPS27.Cancer & metabolism · 2024Article
- CPS1 augments hepatic glucagon response through CaMKII/FOXO1 pathway.Frontiers in pharmacology · 2024Article
- Direct-Acting Antiviral Drug Modulates the Mitochondrial Biogenesis in Different Tissues of Young Female Rats.International journal of molecular sciences · 2023Article
- Heterocyclic amines reduce insulin-induced AKT phosphorylation and induce gluconeogenic gene expression in human hepatocytes.Archives of toxicology · 2023Article
- Regulation of Liver Glucose and Lipid Metabolism by Transcriptional Factors and Coactivators.Life (Basel, Switzerland) · 2023Review
- Microsomal Prostaglandin E Synthase-1 and -2: Emerging Targets in Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2023Review
- The phosphorylation of AMPKβ1 is critical for increasing autophagy and maintaining mitochondrial homeostasis in response to fatty acids.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Reactive Oxygen Species and Oxidative Stress in the Pathogenesis of MAFLD.Journal of clinical and translational hepatology · 2022Review
- Article
- Circadian Regulation and Clock-Controlled Mechanisms of Glycerophospholipid Metabolism from Neuronal Cells and Tissues to Fibroblasts.Molecular neurobiology · 2022Review
- Analysis of Gene Expression Profiles in the Liver of Rats With Intrauterine Growth Retardation.Frontiers in pediatrics · 2022Article
- Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes.Diabetologia · 2021Article
- Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice.Nutrients · 2021Article
- Hepatic transcriptional responses to fasting and feeding.Genes & development · 2021Review
- Article
- Epigenetics of Hepatic Insulin Resistance.Frontiers in endocrinology · 2021Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveThe peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 family of transcriptional coactivators controls hepatic function by modulating the expression of key metabolic enzymes. Hepatic gain of function and complete genetic ablation of PGC-1alpha show that this coactivator is important for activating the programs of gluconeogenesis, fatty acid oxidation, oxidative phosphorylation, and lipid secretion during times of nutrient deprivation. However, how moderate changes in PGC-1alpha activity affect metabolism and energy homeostasis has yet to be determined. RESEARCH DESIGN AND
methodsTo identify key metabolic pathways that may be physiologically relevant in the context of reduced hepatic PGC-1alpha levels, we used the Cre/Lox system to create mice heterozygous for PGC-1alpha specifically within the liver (LH mice).
resultsThese mice showed fasting hepatic steatosis and diminished ketogenesis associated with decreased expression of genes involved in mitochondrial beta-oxidation. LH mice also exhibited high circulating levels of triglyceride that correlated with increased expression of genes involved in triglyceride-rich lipoprotein assembly. Concomitant with defects in lipid metabolism, hepatic insulin resistance was observed both in LH mice fed a high-fat diet as well as in primary hepatocytes.
conclusionsThese data highlight both the dose-dependent and long-term effects of reducing hepatic PGC-1alpha levels, underlining the importance of tightly regulated PGC-1alpha expression in the maintenance of lipid homeostasis and glucose metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.