Chemical activators of BSCL2 lipid droplet biogenesis associated, seipin, operate through various pathways to modulate its activity in lipid droplet formation and maintenance. Oleic Acid, for instance, directly interacts with the lipid monolayer of droplets, influencing their curvature and surface tension, which in turn can activate seipin's functional role in lipid droplet dynamics. Similarly, Arachidonic Acid, by integrating into lipid membranes, may engage signaling pathways that regulate lipid droplet formation, thereby facilitating the activation of seipin.
On the other hand, several chemicals function through peroxisome proliferator-activated receptor (PPAR) pathways to activate seipin. Pioglitazone and Rosiglitazone are PPAR-gamma agonists that enhance the transcription of genes involved in adipocyte differentiation and lipid metabolism, which can lead to seipin activation due to its role in lipid droplet formation. Clofibrate and Gemfibrozil, both PPAR-alpha agonists, and Bezafibrate, a pan-PPAR agonist, stimulate lipid metabolism pathways that necessitate increased lipid droplet formation, thus activating seipin. PPAR-delta agonists like L-165041 and GW501516 lead to heightened fatty acid oxidation and energy expenditure, which can prompt seipin's role in managing lipid droplet formation in metabolically active tissues. Additionally, GW7647, another PPAR-alpha agonist, triggers similar metabolic processes, thereby facilitating seipin's activation. Lastly, Telmisartan, while primarily an angiotensin II receptor blocker, also partially activates PPAR-gamma, which can lead to increased lipid storage and seipin activation in its capacity to manage lipid droplet dynamics.
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