PPARA (Peroxisome Proliferator Activated Receptor Alpha)

In FFA-treated HepG2 cells, both SGB121 and F1 decreased reactive oxygen species (ROS), suppressed sterol regulatory element-binding protein 1 (SREBP1), enhanced peroxisome proliferator-activated receptor-α (PPARα) and β-oxidation, and restored insulin receptor substrate (IRS)/protein kinase B (Akt)/glucose transporter 2 (GLUT2) signaling. SGB121 ameliorates MAFLD and related metabolic dysfunction through antioxidant, lipid-regulating, and insulin-sensitizing actions, highlighting its potential as a safe multifunctional nutraceutical for MAFLD management.

These findings demonstrate that CB-839 exhibits significant antifibrotic effects in a rat model of liver fibrosis, primarily by modulating glutamine metabolism and key fibrotic biomarkers. CB-839 has the potential to be a promising therapeutic approach for liver fibrosis.

Taken together, our studies indicate that LON can suppress AD-like skin inflammation both in vivo and in vitro. These findings imply that LON may serve as a possible alternative therapeutic treatment for AD or other skin-related inflammatory diseases.

Moreover, the correlation of PPARs with ACSL4 highlights the possible role of PPAR-α and PPAR-γ in the regulation of tumor tissue ferroptosis and suggests that targeting these pathways could offer new therapeutic strategies for managing breast cancer. However, further studies are needed to understand the mechanism of action.

The alleviating effect of PG on QDLC may be attributed to the activation of the HIF-1α/PPARα-mediated FAO signaling axis, which improves mitochondrial dysfunction in the liver.

Mitochondrial injury was characterized by reduced carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor alpha, with increased hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A. In patients with cirrhosis, impaired cardiac function and elevated brain natriuretic peptide levels correlated with total bilirubin. The progression of CCM is closely associated with cirrhosis severity and appears to be driven by myocardial atrophy, apoptosis, inflammation, fibrosis, and mitochondrial dysfunction.

Concurrently, 1d exhibits potent anti-inflammatory effects in both settings, effectively mitigating hepatic inflammation in a MASH mouse model. Therefore, compound 1d improves lipid metabolism through the AMPK-ACC-PPARα axis and additionally provides an anti-inflammatory benefit, highlighting its potential as a novel therapeutic candidate for MASH.

Wnt/β-catenin signaling could be a potential lymphomagenetic mechanism for extranodal infiltration of T-lymphoblastic lymphoma. Fenofibrate has the potential to be an effective therapeutic strategy against liver infiltration of T-lymphoblastic lymphoma in MASH liver.

Conversely, conjugated linoleic acid (CLA), a healthy fatty acid, enhances PPARα and P53 transactivation while inhibiting PPARδ transactivation, leading to decreased CD73 and increased TRAIL-R1/2, which enhances anti-tumor immunity and limits metastasis. These findings suggest a direct, universal mechanism by which fatty acid composition regulates immune homeostasis and tumor progression via PPARα/δ-P53 crosstalk.

These findings establish a γ-H2AX-PPARα signaling axis that promotes HBV transcription and demonstrate that caffeine interferes with this pathway. In summary, our study demonstrated that γ-H2AX may serve as a nutritionally targetable node, supporting dietary and adjunct strategies for HBV management.

Cytotoxicity varied by compound, while the PPARγ agonist pioglitazone and the PPARα agonist fenofibrate were preferentially active in CTC lines, DG172 hydrochloride was selective for pleural effusion-derived lines, while rosiglitazone maleate, cloxiquine, and agrimol B showed no selectivity. These findings support PPARs as clinically relevant targets in SCLC, with PPAR-directed agents showing cytotoxic effects comparable to those reported in other malignancies. Such agents may aid SCLC treatment and help delineate biological differences between CTCs and resident tumor cells.

Its involvement in cancer development offers new biological insights and potential therapeutic strategies. As a potential biomarker and therapeutic target, it presents novel approaches for the clinical management of CRC.