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Adrenoceptor‐related decrease in serum triglycerides is independent of PPAR α activation
Author(s) -
Konstandi Maria,
Kypreos Kyriakos E.,
Matsubara Tsutomu,
Xepapadaki Eva,
Shah Yatrik M.,
Krausz Kristopher,
Andriopoulou Christina E.,
Kofinas Aristeidis,
Gonzalez Frank J.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14966
Subject(s) - medicine , endocrinology , chemistry , stimulation , lipoprotein lipase , triglyceride , phenylephrine , lipid metabolism , adipose tissue , cholesterol , biology , blood pressure
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, α 1 ‐ AR s were activated with phenylephrine ( PH ) and β 1/2 ‐ AR s with isoprenaline ( ISOP ). Both AR agonists markedly reduced serum TG levels independently of PPAR α activation. These drugs also significantly activated the hormone‐sensitive lipase in the white adipose tissue indicating increased mobilization of TG s 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/ PI 3k/ 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 α 1 ‐ and β 1/2 ‐ AR s 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 PPAR α independent mechanisms.