ArticlePloS one2014
Short term feeding of a high fat diet exerts an additive effect on hepatocellular damage and steatosis in liver-specific PTEN knockout mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Phase II Investigation of TVB-2640 (Denifanstat) with Bevacizumab in Patients with First Relapse High-Grade Astrocytoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Pharmacological Potential of Selenoproteins in the Regulation of Oxidative Stress in Liver Diseases.Pharmaceutics · 2026Review
- Deficiency of PTEN Confers Hypersensitivity to Fatty Acid-Mediated ER Stress in Transformed Hepatocytes.International journal of molecular sciences · 2026Article
- Bibliometrics-guided cyberpharmacology and transcriptomics for multidimensional analysis of the antihepatic fibrosis mechanism of kaempferol.Frontiers in molecular biosciences · 2025Article
- Impact of Serotonin Transporter Absence on Brain Insulin Receptor Expression, Plasma Metabolome Changes, and ADHD-like Behavior in Mice fed a Western Diet.Biomolecules · 2024Article
- Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.Frontiers in oncology · 2022Review
- Close interactions between lncRNAs, lipid metabolism and ferroptosis in cancer.International journal of biological sciences · 2021Review
- Cholestatic liver disease results increased production of reactive aldehydes and an atypical periportal hepatic antioxidant response.Free radical biology & medicine · 2019Article
- Ezetimibe suppresses development of liver tumors by inhibiting angiogenesis in mice fed a high-fat diet.Cancer science · 2019Article
- Signaling through non-membrane nuclear phosphoinositide binding proteins in human health and disease.Journal of lipid research · 2019Review
- The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?Cellular and molecular life sciences : CMLS · 2018Review
- Altered global microRNA expression in hepatic stellate cells LX-2 by angiotensin-(1-7) and miRNA-1914-5p identification as regulator of pro-fibrogenic elements and lipid metabolism.The international journal of biochemistry & cell biology · 2018Article
- PTEN: Tumor Suppressor and Metabolic Regulator.Frontiers in endocrinology · 2018Review
- High-fat diet modifies expression of hepatic cellular senescence gene p16(INK4a) through chromatin modifications in adult male rats.Genes & nutrition · 2018Article
- Elevated Nrf-2 responses are insufficient to mitigate protein carbonylation in hepatospecific PTEN deletion mice.PloS one · 2018Article
- Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH.Free radical biology & medicine · 2017Article
- Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.BioMed research international · 2017Article
- Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats.Oxidative medicine and cellular longevity · 2017Article
- Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice.Redox biology · 2016Article
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8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundHepatospecific deletion of PTEN results in constitutive activation of Akt and increased lipogenesis. In mice, the addition of a high fat diet (HFD) downregulates lipogenesis. The aim of this study was to determine the effects of a HFD on hepatocellular damage induced by deletion of PTEN.
methods12 Week old male flox/flox hepatospecific PTEN mice (PTENf/f) or Alb-Cre controls were fed a HFD composed of 45% fat-derived calories (from corn oil) or a normal chow. Animals were then analyzed for hepatocellular damage, oxidative stress and expression of enzymes involved in fatty acid metabolism.
resultsIn the Alb-Cre animals, the addition of a HFD resulted in a significant increase in liver triglycerides and altered REDOX capacity as evidenced by increased GPX activity, decreased GST activity and decreased hepatic concentrations of GSSG. In addition, SCD2, ACLY and FASN were all downregulated by the addition of HFD. Furthermore, expression of PPARα and PPARα-dependent proteins Cyp4a and ACSL1 were upregulated. In the PTENf/f mice, HFD resulted in significant increased in ALT, serum triglycerides and decreased REDOX capacity. Although expression of fatty acid synthetic enzymes was elevated in the chow fed PTENf/f group, the addition of HFD resulted in SCD2, ACLY and FASN downregulation. Compared to the Alb-Cre HFD group, expression of PGC1α, PPARα and its downstream targets ACSL and Cyp4a were upregulated in PTENf/f mice.
conclusionsThese data suggest that during conditions of constitutive Akt activation and increased steatosis, the addition of a HFD enhances hepatocellular damage due to increased CD36 expression and altered REDOX status. In addition, this work indicates HFD-induced hepatocellular damage occurs in part, independently of Akt signaling.
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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.