Publications by authors named "P Degrace"
Article Synopsis
- - The study investigates the role of the enzyme ELOVL5 in the biosynthesis of Polyunsaturated Fatty Acids (PUFAs) and its implications for liver conditions, specifically MASH (metabolic-associated steatotic liver disease), revealing how enzyme disruption affects liver metabolism.
- - Research showed that ELOVL5 levels increase during MASH progression and that its absence in mice leads to significant liver issues after a high-fat, high-sucrose diet, including fat accumulation, inflammation, and fibrosis.
- - The findings suggest that the loss of ELOVL5 disrupts mitochondrial function, contributes to liver damage from dietary factors, and alters fatty acid metabolism, indicating a critical link between enzyme activity and liver health.
Article Synopsis
- The study investigated the effects of INV-202, a new cannabinoid type-1 receptor inverse agonist, on kidney function in a mouse model of type-1 diabetes induced by streptozotocin.
- Mice were treated with various doses of INV-202 for 28 days, showing decreased urinary urea and albumin excretion compared to untreated diabetic mice, along with improvements in the urinary albumin to creatinine ratio.
- INV-202 also reduced kidney weight and podocyte loss, restored gene expression for podocyte proteins, and decreased levels of angiotensin II, indicating potential benefits for diabetic nephropathy.
Article Synopsis
- Pharmacological inhibition of mitochondrial fatty acid oxidation (FAO) can help treat metabolic diseases but also triggers the activation of the mTORC1 pathway, promoting protein synthesis and tissue growth.
- The study found that this activation occurs due to the acetylation of Raptor, a key protein in the mTORC1 pathway, mediated by increased levels of acetyl-CoA when FAO is inhibited.
- The researchers identified histone deacetylase 7 as a potential regulator of Raptor, highlighting the intricate relationship between nutrient metabolism and protein acetylation in the context of mitochondrial FAO inhibition.
Chemical Synthesis, Pharmacokinetic Properties and Biological Effects of JM-00266, a Putative Non-Brain Penetrant Cannabinoid Receptor 1 Inverse Agonist.
Tania Muller Laurent Demizieux Stéphanie Troy-Fioramonti Chloé Buch Julia Leemput Patricia Passilly-Degrace Pascal Degrace
Int J Mol Sci
March 2022
Article Synopsis
- Researchers developed JM-00266, a new cannabinoid 1 receptor (CB1R) blocker with limited ability to cross the blood-brain barrier, aimed at treating metabolic disorders linked to obesity.
- Unlike its predecessor Rimonabant, JM-00266 does not affect central behaviors like food intake and anxiety, indicating it primarily acts in the periphery.
- JM-00266 enhances glucose tolerance and insulin sensitivity in mice and promotes fat breakdown in adipose tissue, suggesting its potential for managing obesity-related metabolic issues.
Article Synopsis
- White adipose tissue (WAT) contains an endocannabinoid system (ECS) that produces endocannabinoids like AEA and 2-AG, which are believed to regulate fat storage and tissue functions but have an unclear role in lipid mobilization.
- In experiments, increasing ECS activity in WAT led to higher levels of 2-AG, which decreased lipolysis (the breakdown of fat) in both lean and obese mice, indicating that ECS may suppress fat mobilization.
- Despite the ineffective results of acute CB1R blockade on lipolysis in obese subjects, the findings suggest that ECS activation in WAT could contribute to tissue changes that potentially lead to organ dysfunction in obesity.