Article
Pharmacology & Pharmacy
Amir Hossein Faghfouri, Yaser Khajebishak, Laleh Payahoo, Elnaz Faghfuri, Mohammadreza Alivand
Summary: Autophagy pathways are involved in the pathogenesis of some obesity related health problems. PPAR-gamma as the main modulator of adipogenesis process can be effective in regulating obesity related phenotypes. The effects of PPAR-gamma and its agonists on autophagy modulation in obesity have been investigated in a limited number of studies.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Oncology
Tiange Chi, Mina Wang, Xu Wang, Ke Yang, Feiyu Xie, Zehuan Liao, Peng Wei
Summary: PPARs are lipid sensors and metabolic regulators, with PPAR-γ showing potential in inhibiting cell proliferation, inducing apoptosis, and disrupting inflammation. However, safety concerns including drug interactions need to be addressed for clinical applications.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Fengyu Huang, Zhiping Zeng, Weidong Zhang, Zhiqiang Yan, Jiayun Chen, Liangfa Yu, Qian Yang, Yihuan Li, Hongyu Yu, Junjie Chen, Caisheng Wu, Xiao-Kun Zhang, Ying Su, Hu Zhou
Summary: This study highlights the importance of meta-substitution in benzylidene moiety for PPARγ binding and activation, and the essential role of indene fluorine in regulating PPARγ. Compound 6b showed significant improvement in glucose tolerance in a diabetic model and exhibited no apparent toxicity to osteoblastic formation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jingjing Li, Chuanyong Guo, Jianye Wu
Summary: Liver fibrosis is a common process in the development of liver diseases to cirrhosis. The activation of Peroxisome proliferator-activated receptors (PPARs) plays a crucial role in fibrosis by regulating downstream pathways. Research on PPAR-γ ligands and other novel drugs has become a focus in recent years for potential treatment of liver fibrosis.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Review
Nutrition & Dietetics
Yushu Qin, Donalyn Bily, Makayla Aguirre, Ke Zhang, Linglin Xie
Summary: The increasing incidence of pregnancy complications, such as gestational diabetes mellitus and preeclampsia, is a cause for concern. The pathogenesis of these complications involves the pathological placenta, and the transcription factor PPARγ may have a critical role. While PPARγ agonists show potential in treating preeclampsia, their safety during pregnancy is not yet established.
Review
Pharmacology & Pharmacy
Bianca Seminotti, Mateus Grings, Jerry Vockley, Guilhian Leipnitz
Summary: Inherited metabolic disorders (IMDs) are genetic disorders that disrupt specific metabolic pathways, leading to biochemical, clinical, and pathophysiological consequences. Secondary mitochondrial dysfunction, particularly oxidative phosphorylation impairment and elevated reactive oxygen species, has been found to play a crucial role in many of these disorders. Peroxisomal proliferator-activated receptors (PPARs), a group of nuclear hormone receptors, regulate various cellular functions and processes, including oxidative stress response, inflammation, lipid metabolism, and mitochondrial bioenergetics. Activation of PPARs has shown to improve oxidative phosphorylation and reduce reactive species levels, making pharmacological treatment with PPAR activators a promising approach for IMDs. This review summarizes preclinical and clinical data on the effects of PPARs in IMDs.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Pilar Pizcueta, Cristina Vergara, Marco Emanuele, Anna Vilalta, Laura Rodriguez-Pascau, Marc Martinell
Summary: Increasing evidence suggests that PPAR gamma plays an important role in CNS physiology and is involved in cellular metabolism and repair. However, most PPAR gamma agonists have failed to show efficacy in clinical trials of neurodegenerative diseases, possibly due to insufficient brain exposure. Leriglitazone, a BBB-penetrant PPAR gamma agonist, is being developed as a potential treatment for CNS diseases. This review discusses the main roles of PPAR gamma, mechanism of action of PPAR gamma agonists, and the evidence supporting the use of leriglitazone.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andrzej T. Slominski, Tae-Kang Kim, Radomir M. Slominski, Yuwei Song, Shariq Qayyum, Wojciech Placha, Zorica Janjetovic, Konrad Kleszczynski, Venkatram Atigadda, Yuhua Song, Chander Raman, Cornelis J. Elferink, Judith Varady Hobrath, Anton M. Jetten, Russel J. Reiter
Summary: Melatonin and its metabolites have various effects, including interactions with AhR and PPAR γ. They can reduce cellular damage at high concentrations and serve as therapeutic agents for skin diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Environmental
Yaqiang Cao, Yuanyuan Chen, Ke Miao, Shuyi Zhang, Fuchang Deng, Mu Zhu, Chao Wang, Wen Gu, Yixuan Huang, Zijin Shao, Xiaoyan Dong, Yufeng Gong, Hui Peng, Hui Yang, Yi Wan, Xudong Jia, Song Tang
Summary: Mounting evidence shows the close association between ambient PM2.5 exposure and obesity development, with adipose tissue being an important target. This study employed a preadipocyte differentiation model to comprehensively explore the adipogenic potential of PM2.5. PM2.5 exposure significantly increased fatty acid uptake, lipid accumulation, and adipogenic differentiation in a concentration-dependent manner. Transcriptome and lipidome analyses revealed disruption of transcriptional and lipid profiling at 10 μg/mL PM2.5. Activation of the peroxisome proliferator-activated receptor (PPAR) pathway and metabolism of glycerophospholipids, glycerolipids, and sphingolipids were most affected during adipocyte differentiation. The study demonstrated that PM2.5 promoted adipogenesis by activating PPAR. through reporter gene assays. The findings provide insights into PM2.5-induced adipogenesis and potential biomolecular targets for preventing PM2.5-induced obesity and related metabolic diseases.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Laya Pourazadi, Mohsen Sharafi, Mohammad Amir Karimi Torshizi, Abdolhossein Shahverdi, AliReza Alizadeh
Summary: This study investigated the effects of pioglitazone on aged broiler breeder roosters and found that pioglitazone supplementation improved sperm motility, mitochondrial activity, and apoptosis rates. These improvements were associated with the receptor-independent actions of pioglitazone, and the mechanism of action of pioglitazone was not affected by the PPAR-γ receptor in broiler breeder roosters.
Article
Chemistry, Medicinal
Zongtao Zhou, Qiang Ren, Shixuan Jiao, Zongyu Cai, Xinqian Geng, Liming Deng, Bin Wang, Lijun Hu, Luyong Zhang, Ying Yang, Zheng Li
Summary: A new quadruple FFA1/PPAR-alpha/gamma/delta agonist, ZLY18, with longer metabolic half-life and stronger lipid-lowering effects, has been discovered for the treatment of NAFLD and NASH. It also exhibits stronger regulation on genes related to lipid synthesis, oxidative stress, inflammation, and fibrosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Juan Sun, Han-Yu Liu, Yi-Heng Zhang, Ze-Yu Fang, Peng-Cheng Lv
Summary: A series of novel TZD analogues were developed, among which 4 g showed promising anti-hyperglycemic and anti-inflammatory activities, potentially serving as a PPAR gamma agonist deserving further investigation.
BIOORGANIC CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Alexandre Vallee, Jean-Noel Vallee, Alain Le Blanche, Yves Lecarpentier
Summary: Endometriosis is a common gynecological disease characterized by inflammation, angiogenesis, invasion, adhesion, and apoptosis. The introduction of new agents like PPAR gamma ligands may be effective in improving the condition of patients, although data in humans remain limited.
Review
Pharmacology & Pharmacy
Sumit Jamwal, Jennifer K. Blackburn, John D. Elsworth
Summary: Neurodegenerative diseases are characterized by the progressive loss of neuron structure and function. Current therapy mainly focuses on symptomatic treatment, but targeting biochemical factors in mitochondria may offer promising treatment options. PPAR gamma-PGC1 alpha plays a crucial role in regulating mitochondrial biogenesis and has been studied in clinical trials for PD, AD, and HD.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Halima Usman, Zhen Tan, Mehreen Gul, Sajid Rashid, Tahir Ali, Fawad Ali Shah, Shupeng Li, Jing Bo Li
Summary: The study identifies rabeprazole and ethambutol as potential agents for the treatment of ischemic stroke. These drugs showed neuroprotective effects by regulating inflammation and cellular survival through PPAR gamma activation.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)