ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2018
High Fat Diet Upregulates Fatty Acid Oxidation and Ketogenesis via Intervention of PPAR-γ.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers, 2 of them syntheses that pooled it.
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Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Gene expression profiling of host lipid metabolism in SARS-CoV-2 infected patients: a systematic review and integrated bioinformatics analysis.BMC infectious diseases · 2024Pooled it
- G Allele of the rs1801282 Polymorphism in PPARγ Gene Confers an Increased Risk of Obesity and Hypercholesterolemia, While T Allele of the rs3856806 Polymorphism Displays a Protective Role Against Dyslipidemia: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2022Pooled it
- Apabetalone Drives a Metabolic Shift Towards Ketogenesis and Reduces Liver Steatosis in Diet-Induced Obesity Mice.Biomedicines · 2026Article
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- Diquat-induced organ toxicity: a focus on regulated cell death pathways and mitochondrial dysfunction.Frontiers in cell and developmental biology · 2026Review
- Cardiac sodium-glucose co-transporter 1 (SGLT1) contributes to heart failure in a mouse model of diabetic cardiomyopathy.Basic research in cardiology · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Electroacupuncture improves cardiac function in hyperlipidemic rats by enhancing efferocytosis in myocardial macrophages via the PPARγ-LXRα-MerTK pathway.Journal of traditional and complementary medicine · 2025Article
- Metagenomic and Metabolomic Profiling Reveals the Impact of High-Fat Diet on Malignant Pleural Effusion.Thoracic cancer · 2025Article
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Xinfeng Capsule inhibits oxidative stress via regulating the PPARγ/ Hmgcs2 signaling pathway in lung tissue of adjuvant arthritis rats.Frontiers in pharmacology · 2025Article
- High-fat diet-induced dyslipidemia drives retinal ECE-1 and ET-1 upregulation.Frontiers in endocrinology · 2025Article
- Identification of Fatty Acid Metabolism Disorder-Related Gene Signature in Septic Cardiomyopathy.Journal of inflammation research · 2025Article
- Comprehensive characterization and metabolomics to explore the role of hydrocortisone-induced yin deficiency syndrome in mice.Biochemistry and biophysics reports · 2024Article
- Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction.Diabetes, obesity & metabolism · 2024Article
- Very Low Calorie Ketogenic Diet: What Effects on Lipid Metabolism?Current nutrition reports · 2024Review
- The Long Non-Coding RNA Obesity-Related (Obr) Contributes To Lipid Metabolism Through Epigenetic Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The transcript level of long non-coding RNAs; MALAT1 and TUG1, and the association with metabolic syndrome-related parameters in women with overweight and obesity.Journal of diabetes and metabolic disorders · 2024Article
- Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells.BMC veterinary research · 2024Article
- Tissue fibrosis associated depletion of lipid-filled cells.Experimental dermatology · 2024Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedErratum.2020
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND/
aimsSystemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis.
methods8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy. Treatment course was followed by echocardiographic measurements, glycemic and lipid profiling, immunoblot, qPCR and immunohistochemistry (IHC) analysis of PPAR-γ and following mitochondrial metabolic enzymes 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2), mitochondrial β- hydroxy butyrate dehydrogenase (BDH1) and pyruvate dehydrogenase kinase isoform 4 (PDK4). In vivo model was translated in vitro, with neonatal rat cardiomyocytes (NRCM) treated with PPAR-γ agonist/antagonist and PPAR-γ overexpression adenovirus in presence of palmitic acid (PA). Apoptosis was determined in vivo from left ventricular heart by TUNEL assay and immunoblot analysis.
resultsWe found exaggerated circulating ketone bodies production and expressions of the related mitochondrial enzymes HMGCS2, BDH1 and PDK4 in HFD-induced diabetic hearts and in PA-treated NRCM. As a mechanistic approach we found HFD mediated activation of PPAR-γ is associated with the above-mentioned mitochondrial enzymes. HFD-fed PPAR-γ-/-mice display decreased hyperglycemia, hyperlipidemia associated with increased insulin responsiveness as compared to HFD-fed WT mice PPAR-γ-/-HFD mice demonstrated a more robust functional recovery after diabetes induction, as well as significantly reduced myocyte apoptosis and improved cardiac function.
conclusionsPPAR-γ has been described previously to regulate lipid metabolism and adipogenesis. The present study suggests for the first time that increased PPAR-γ expression by HFD is responsible for cardiac dysfunction via upregulation of mitochondrial enzymes HMGCS2, BDH1 and PDK4. Targeting PPAR-γ and its downstream mitochondrial enzymes will provide novel strategies in preventing metabolic and myocardial dysfunction in diabetes mellitus.
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