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Publication : Adrenoceptor-related decrease in serum triglycerides is independent of PPARα activation.

First Author  Konstandi M Year  2019
Journal  FEBS J Volume  286
Issue  21 Pages  4328-4341
PubMed ID  31230416 Mgi Jnum  J:298200
Mgi Id  MGI:6477432 Doi  10.1111/febs.14966
Citation  Konstandi M, et al. (2019) Adrenoceptor-related decrease in serum triglycerides is independent of PPARalpha activation. FEBS J 286(21):4328-4341
abstractText  Adrenoceptor (AR)-linked pathways belong to the major components of the stress response system and are associated with the pathophysiology of diseases within the spectrum of metabolic syndrome. In this study, the role of adrenoceptor stimulation in serum triglyceride (TG) regulation in mice was investigated. For this purpose, alpha1 -ARs were activated with phenylephrine (PH) and beta1/2 -ARs with isoprenaline (ISOP). Both AR agonists markedly reduced serum TG levels independently of PPARalpha activation. These drugs also significantly activated the hormone-sensitive lipase in the white adipose tissue indicating increased mobilization of TGs in this tissue. In addition, PH and ISOP up-regulated Lpl, Nr4A, Dgat1, Mttp, Aadac and Cd36 genes, critical in TG regulation, whereas the observed decrease in serum TG levels was independent of the hepatic very low-density lipoprotein (VLDL)-TG secretion. Interestingly, PH and ISOP also inactivated the hepatic insulin/PI3k/AKT/FoxO1 signaling pathway, holding a critical role in the regulation of genes involved in TG synthesis. Taken together, the findings of the present study indicate that stimulation of alpha1 - and beta1/2 -ARs markedly reduced serum TG steady-state levels as a result of alterations in TG synthesis, uptake, transport, hydrolysis, metabolism and clearance, an effect induced by PPARalpha independent mechanisms.
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