Pparg, peroxisome proliferator-activated receptor gamma, is a receptor crucial for controlling cellular metabolism. It regulates the function of immune and stromal cells and is involved in multiple biological processes, such as anti-inflammatory and neuroprotective pathways, as well as lipid and glucose metabolism [1,2]. Genetic studies on its polymorphisms have been used to explore its role in diseases [4-6].

In rheumatoid arthritis (RA), PPARG promotes autophagy to accelerate reactive oxygen species (ROS) clearance, inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation, thus alleviating inflammation. CBD can act as a PPARG agonist to mitigate RA's inflammatory progression [1]. In major depression, the PPARg system has anti-inflammatory and neuroprotective effects in the CNS, increasing BDNF levels, promoting neuroplasticity and neurogenesis, and potentially having antidepressant effects [2]. In adrenal Cushing's syndrome, PPARG and related genes are downregulated, and its activator rosiglitazone decreases cell viability and steroid production, suggesting its potential as a therapeutic target [3]. For type 2 diabetes mellitus (T2DM), the rs1801282 (Pro12Ala) variant in PPARG is associated with a decreased risk of T2DM, and patients with the Ala12 variant may respond better to thiazolidinediones treatment [4,5]. In bladder cancer, Pparg signaling controls cancer subtype and immune exclusion, being downregulated in basal (muscle-invasive) and amplified in luminal (non-muscle-invasive) subtypes [6]. In psoriasis vulgaris, enhanced PPARG gene expression is a protective factor, indicating it as a potential therapeutic target [7]. In hypopharyngeal squamous cell carcinoma (HSCC), PPARG may promote chemosensitivity, likely by affecting cell proliferation and motility pathways [8].

In summary, Pparg plays essential roles in multiple biological processes and disease conditions. Studies on its genetic variants and functions in various disease models, especially in relation to inflammation, metabolism, and cancer, have provided insights into potential therapeutic strategies targeting Pparg.

References:

1. Geng, Qishun, Xu, Jiahe, Cao, Xiaoxue, Jia, Lansi, Xiao, Cheng. 2024. PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis. In Journal of autoimmunity, 146, 103214. doi:10.1016/j.jaut.2024.103214. https://pubmed.ncbi.nlm.nih.gov/38648706/

2. Gold, Philip W. 2021. The PPARg System in Major Depression: Pathophysiologic and Therapeutic Implications. In International journal of molecular sciences, 22, . doi:10.3390/ijms22179248. https://pubmed.ncbi.nlm.nih.gov/34502154/

3. Vetrivel, Sharmilee, Tamburello, Mariangela, Oßwald, Andrea, Sbiera, Silviu, Riester, Anna. 2023. PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome. In Frontiers in endocrinology, 14, 1265794. doi:10.3389/fendo.2023.1265794. https://pubmed.ncbi.nlm.nih.gov/38098864/

4. Sarhangi, Negar, Sharifi, Farshad, Hashemian, Leila, Aghaei Meybodi, Hamid Reza, Hasanzad, Mandana. 2020. PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis. In Scientific reports, 10, 12764. doi:10.1038/s41598-020-69363-7. https://pubmed.ncbi.nlm.nih.gov/32728045/

5. Jang, Eun Jeong, Lee, Da Hoon, Im, Sae-Seul, Yee, Jeong, Gwak, Hye Sun. 2023. Correlation between PPARG Pro12Ala Polymorphism and Therapeutic Responses to Thiazolidinediones in Patients with Type 2 Diabetes: A Meta-Analysis. In Pharmaceutics, 15, . doi:10.3390/pharmaceutics15061778. https://pubmed.ncbi.nlm.nih.gov/37376225/

6. Tate, Tiffany, Xiang, Tina, Wobker, Sarah E, Mckiernan, James M, Mendelsohn, Cathy Lee. 2021. Pparg signaling controls bladder cancer subtype and immune exclusion. In Nature communications, 12, 6160. doi:10.1038/s41467-021-26421-6. https://pubmed.ncbi.nlm.nih.gov/34697317/

7. Xue, Yan, Xia, Yuning, Cheng, Donghao, Mei, Ping, Hong, Sheng. 2024. Association between genetically proxied PPARG activation and psoriasis vulgaris: a Mendelian randomization study. In The Journal of dermatological treatment, 35, 2381763. doi:10.1080/09546634.2024.2381763. https://pubmed.ncbi.nlm.nih.gov/39034037/

8. Lian, Meng, Chen, Jiaming, Shen, Xixi, Hou, Lizhen, Fang, Jugao. 2020. Pparg may Promote Chemosensitivity of Hypopharyngeal Squamous Cell Carcinoma. In PPAR research, 2020, 6452182. doi:10.1155/2020/6452182. https://pubmed.ncbi.nlm.nih.gov/32373170/