Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in both developmental and metabolic functions. There are activated by fatty acids, fatty acid metabolites, and synthetic compounds marketed for their lipid-lowering and antidiabetic actions. It was clearly established that activation of PPAR alpha and PPAR gamma, by fibrates and thiazolidinediones, respectively, impair metabolic disorders. The implication of the third member of the PPAR family, PPAR delta, remained evasive until recently. These past few years, it has been demonstrated that treatment with PPAR delta agonists normalizes blood lipids, reduces insulin resistance and adiposity in rodent and primate. Utilization of both cellular and animal models revealed that the nuclear receptor plays a central role in the control of fatty acid burning in adipose tissue and skeletal muscle. Furthermore, PPAR delta appeared to be important for adaptive response of skeletal muscle to environmental changes, such as physical exercise.
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http://dx.doi.org/10.1016/j.biochi.2004.11.009 | DOI Listing |
Front Immunol
January 2025
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
The treatment of fungal keratitis(FK) remains challenging due to delayed fungal detection and the limited effectiveness of antifungal drugs. Fungal infection can activate both innate and adaptive immune responses in the cornea. Fungi stimulate the production of oxidative stress-related biomarkers and mediate the infiltration of neutrophils, macrophages, and T cells.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Pharmacology, KLE College of Pharmacy KAHER, A Constituent Unit of KAHER-Belagavi University, Rajajinagar, Bengaluru, Karnataka, India.
Liver cancer is one of the most prevalent malignant diseases in humans and the second leading cause of cancer-related mortality globally. Angiopteris helferiana was mentioned as a possible anticancer herb according to ethnomedicinal applications. However, the molecular docking and chemical profiling of the bioactive phytoconstituents accountable for the reported anticancer action still require research.
View Article and Find Full Text PDFBioorg Chem
January 2025
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Future Medicine Co., Ltd, 54 Changup-ro, Sujeong-gu, Seongnam, Gyeonggi-do 13449, Republic of Korea. Electronic address:
This study explores the synthesis and evaluation of truncated 1'-homologated 4'-selenonucleosides as dual modulators of PPARγ and PPARδ. Starting with d-lyxose, a 4'-selenosugar was synthesized and condensed with a nucleobase via an S2 reaction, followed by modifications at the C2- and N-positions, yielding compounds 3a-l. Structure-activity trend analysis identified compound 3h, featuring 2-chloro and N-3-iodobenzylamine substituents, as a potent PPARγ partial agonist and PPARδ antagonist (PPARγ K = 2.
View Article and Find Full Text PDFHepatol Commun
January 2025
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.
Cell Commun Signal
December 2024
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, 08028, Spain.
Background: The increased degradation of the insulin receptor β subunit (InsRβ) in lysosomes contributes to the development of insulin resistance and type 2 diabetes mellitus. Endoplasmic reticulum (ER) stress contributes to insulin resistance through several mechanisms, including the reduction of InsRβ levels. Here, we examined how peroxisome proliferator-activated receptor (PPAR)β/δ regulates InsRβ levels in mouse skeletal muscle and C2C12 myotubes exposed to the ER stressor tunicamycin.
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