Chemical activators of KLF14 can influence the protein's activity through various metabolic pathways. Metformin, AICAR, and Berberine are known to activate AMP-activated protein kinase (AMPK), a crucial energy sensor in the cell that helps regulate metabolic processes. Activation of AMPK by these chemicals can lead to downstream effects that enhance the function of KLF14, which plays a significant role in lipid metabolism and glucose regulation. By activating AMPK, these compounds can indirectly promote the activity of KLF14 within these metabolic pathways. Similarly, Epigallocatechin gallate (EGCG), through its interaction with AMPK, can also support the functional activation of KLF14 by modulating metabolic regulatory networks.
Furthermore, the polyphenolic compound Resveratrol and the flavonoid Quercetin activate SIRT1, an NAD+-dependent deacetylase involved in cellular stress responses and metabolic regulation. SIRT1 activation can lead to changes in the activity of various transcription factors and co-regulators that are involved in metabolic pathways where KLF14 is a key regulatory element. Through these changes, KLF14 activity can be enhanced, especially in pathways governing lipid and glucose metabolism. PPAR agonists, such as Pioglitazone, Rosiglitazone, Fenofibrate, Troglitazone, and Oleoylethanolamide (OEA), modulate peroxisome proliferator-activated receptors, which are nuclear receptors that play essential roles in the regulation of metabolic functions. These agonists may indirectly enhance KLF14 function by influencing the transcription of genes involved in glucose and lipid metabolism, thereby modulating the activity of KLF14. Retinoic Acid also modulates gene expression through its receptors and could indirectly influence KLF14 activity by affecting cellular processes, including differentiation and metabolism, where KLF14 is implicated in the regulatory network. These chemicals, by targeting specific pathways and processes, can support the functional activation of KLF14.
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