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Open research questions in Peroxisome Proliferator-Activated Receptors

95 gap statements mined from Peroxisome Proliferator-Activated Receptors papers in our 4.5M-paper local library, which holds 434 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • 34 35 Although the clinical burden continues to rise, only two FDA- approved treatments— resmetirom and semaglutide—are currently available, and both are limited to adults with MASH and fibrosis with relatively low efficient response and obvious side effects. However, its function in liver metabolism and its relevance to MASH have not been previously investigated.

    Blocking MOXD1-derived ACOX1 peroxisome trafficking suppresses metabolic dysfunction-associated steatohepatitis · 2026 · DOI

  • Genetic differences within fatty acid-binding protein family are an important molecular nexus between type 2 diabetes mellitus and non-alcoholic fatty liver disease. FABP1, FABP2, FABP4 and FABP5 polymorphic altera- tions in lipid transport, insulin signaling and inflamma- tory signaling pathways lead to the metabolic defect that contributes to both conditions. These discoveries high- light the significance of FABPs in the inter-organ commu- nication between the liver, adipose tissue and intestine. In the future, combining genetic, transcriptomic, and metabolomic data will reveal more insights into the pathogenesis of disease by FABP and inter-individual differences in metabolic risk. Precision medicine devel- opments and pharmacogenomics provide the possibility to customize the interventions according to FABP geno- type. Moreover, selective FABP inhibitors and dietary/ lifestyle interventions that are based on FABP-pathways are promising in dual prevention of T2DM and NAFLD. FABPs are potentially useful future therapeutic targets, but more experimental and clinical trials are needed to prove their efficacy in treating mental disorders. FABPs are potentially useful future therapeutic targets, but addi- tional experimental and clinical validation is necessary to prove their effectiveness in treating mental disorders.

    Genetic insights into FABP polymorphisms linking type 2 diabetes mellitus and non-alcoholic fatty liver disease · 2026 · DOI

  • Given that previous studies on the metabolic effects of Sti have largely focused on its cholesterol-lowering and anti-inflam- matory properties (19, 20), and its effects in insulin resistance models have not been systematically reported, the present study fills this gap.

    Stigmasterol ameliorates obesity-associated insulin resistance by activating the PPARγ pathway and alleviating oxidative stress · 2026 · DOI

  • Finally, the exact mechanisms underlying the PPARα agonist-mediated neuropro- tective effects are not fully understood. For instance, whereas a clear role for PPARα in mitochondrial function is supported by several studies, other studies reported conflicting results. Another particularly important issue in pharmacological research is the fact that the majority of in vivo studies, in general, employ male experimental animals, and, therefore, comprehensive knowledge about the effectiveness of PPARα agonists on AD and PD pathology in females is lacking.

    Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies · 2025 · DOI

  • Moreover, the relationship between miR-212-3p-EGR1, miR-222-3p-FOS, and miR-132-3p-EGR1 needs to be validated in large-scale studies of patients with chronic alcoholism to verify their diagnostic value and evaluate their potential clinical significance by comparing their clinical and pathological subnetworks of miRNA-mRNA features. networks should be further explored and verified by in vivo and in vitro studies.

    Analysis of microRNAs and the microRNA-messengerRNA regulatory network in chronic alcohol exposure · 2024 · DOI

  • Thus, the pathology in XALD is limited to a relatively small number of tissue types. Why, therefore, is the pathology in XALD limited to only a few tissue types? A definitive explanation for this remains elusive.

    Role of ACSBG1 in Brain Lipid Metabolism and X-Linked Adrenoleukodystrophy Pathogenesis: Insights from a Knockout Mouse Model · 2024 · DOI

  • However, the impact of FZHY on cholestatic liver disease has not been fully elucidated.

    Fuzheng Huayu formula ameliorates chronic cholestatic liver injury by upregulating PPARa in mice · 2026 · DOI

  • Yet, the details of liver macrophage regulation and their plasticity in MASH pathogenesis remain to be further defined.

    TMEM189/PEDS1 deficiency aggravates MASH progression by promoting FASN-mediated macrophage activation · 2026 · DOI

  • Despite the numerous studies conducted on the influence of pachymic acid on various malignant tumors, potential tar- gets of pachymic acid as well as their binding sites remain to be elucidated.

    Pachymic acid exhibits synergistic antitumor efficacy with lenvatinib in hepatocellular carcinoma by targeting PPARγ to inhibit glycolysis · 2026 · DOI

  • Future research should address these gaps by the intrinsic relationship between this pathway and the occurrence and progression of liver diseases, aiming the development and progression of metabolic diseases mediated by environmental pollutant exposure.

    Mechanism of BaP- regulated hepatic lipid metabolism via AhR activation and AR modulation · 2026 · DOI

  • Domestic chicken provides animal protein for humans and can be used as an excellent animal model for scientific studies; however, only a few studies have reported on the regulation of gene expression in chicken adipose tissue.

    RNA-Seq Analysis Reveals the Molecular Mechanisms Regulating the Development of Different Adipose Tissues in Broiler Chicks · 2024 · DOI

  • Although FDX1 has been extensively characterized biochemically, its role in physiology and lipid metabolism has not been explored.

    Ferredoxin 1 is essential for embryonic development and lipid homeostasis · 2024 · DOI

  • However, the mechanism by which a subset of peroxisomal proteins is transported from the peroxisome to the proteasome for degradation remains unclear.

    CDC48A and the ubiquitin-associated domain protein PUX10 regulate the ubiquitin-dependent degradation of peroxisomal proteins in Arabidopsis · 2026 · DOI

  • However, the role of PPAR-γ in allergic airway inflammation, particularly through regulation of macrophage senescence, remains poorly defined.

    PPAR-γ suppresses macrophage senescence and allergic airway inflammation through controlling lipid metabolic pathways · 2026 · DOI

  • However, the mechanism, by which CETP moves lipids between lipoproteins, and roles of PL plugs in CETP function remain elusive.

    Phospholipids that Plug the Pores of Cholesteryl Ester Transfer Protein Control Its Triglyceride Transfer · 2026 · DOI

  • These findings, combined with its established clinical safety profile, support further investigation of fenofibrate as a potential therapeutic strategy in GBM.

    Fenofibrate as an anti-cancer treatment: an in vitro study on glioblastoma cells at various oxygen levels and on normal astrocytes · 2026 · DOI

  • While PPAR-α and PPAR-γ have been extensively studied in macrophages for their roles in atherosclerosis, the epigenetic regulation of these nuclear receptors under high cholesterol conditions remains poorly understood.

    METTL14 inhibits atherogenesis by epigenetically activating PPAR-α/γ transcription and fatty acid oxidation in VSMCs · 2026 · DOI

  • Although alternatively spliced variants of certain peroxisome-related genes have been identified, the regulatory mechanisms governing alternative splicing (AS) and its functional impact on peroxisomal redox homeostasis remain poorly understood.

    DDX1 crotonylation mediates ACOX1 alternative splicing through HNRNPK to increase peroxisomal oxidative damage · 2025 · DOI

  • The underlying pathophysiology remains unclear, and while elevated oxidative stress and signs of mitochondrial dysfunction have been observed in X-ALD cells and tissues, their precise roles are still uncertain.

    Mitochondrial dysfunction and impaired oxidative stress defense as potential trigger of cerebral X-linked adrenoleukodystrophy · 2025 · DOI

  • The molecular mechanisms whereby differentiated cancer cells switch towards a CSC phenotype are poorly understood.

    PPARγ, a key modulator of metabolic reprogramming, stemness and chemoresistance associated with retrodifferentiation in human hepatocellular carcinomas · 2025 · DOI

  • Background GPR171 suppresses T cell immune responses involved in antitumour immunity, while its role in inflammatory bowel disease (IBD) pathogenesis remains unclear.

    GPR171 restrains intestinal inflammation by suppressing FABP5-mediated Th17 cell differentiation and lipid metabolism · 2025 · DOI

  • Peroxisome proliferator-activated receptor γ (PPARγ) drives urothelial differentiation and UPK expression in other tissues but has not been investigated in the renal urothelium.

    PPARγ promotes urothelial remodeling during urinary tract obstruction · 2025 · DOI

  • While previously reported to repress myogenesis, its role in adipose tissue metabolism remains unclear.

    Ret finger protein deficiency attenuates adipogenesis in male mice with high fat diet-induced obesity · 2025 · DOI

  • BACKGROUND: This study was designed to assess the efficacy of the Jieyu Guben Decoction (JYGBD), a novel formula that has not been reported, in treating rats with combined allergic rhinitis and asthma syndrome (CARAS) and the mechanism.

    Jieyu Guben decoction alleviates combined allergic rhinitis and asthma syndrome by balancing Th17/Treg expression and restoring PPARD · 2025 · DOI

  • However, the mechanism of oxidative stress induction by AR-targeting therapy remains unclear.

    Oxidative stress in peroxisomes induced by androgen receptor inhibition through peroxisome proliferator–activated receptor promotes enzalutamide resistance in prostate cancer · 2024 · DOI

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95 gap statements have been mined from Peroxisome Proliferator-Activated Receptors papers in our 4.5M-paper local library, which holds 434 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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