内分泌学
内科学
化学
氧化磷酸化
产热素
氧化应激
丙二醛
褐色脂肪组织
脂肪组织
生物化学
生物
医学
作者
Aryane Cruz Oliveira Pinho,Diana Santos,Inês Baldeiras,Ana Burgeiro,Ermelindo C. Leal,Eugénia Carvalho
摘要
Introduction Thoracic perivascular adipose tissue (tPVAT) has a phenotype resembling brown AT. Dysfunctional tPVAT appears to be linked to vascular dysfunction. Methods We evaluated uncoupling protein 1 (UCP1) expression by Western blot, oxidative stress by measuring lipid peroxidation, the antioxidant capacity by HPLC and spectrophotometry, and mitochondrial respiration by high-resolution respirometry (HRR) in tPVAT, compared to inguinal white AT (iWAT), obtained from non-diabetic (NDM) and streptozocin-induced diabetic (STZ-DM) mice. Mitochondrial respiration was assessed by HRR using protocol 1: complex I and II oxidative phosphorylation (OXPHOS) and protocol 2: fatty acid oxidation (FAO) OXPHOS. OXPHOS capacity in tPVAT was also evaluated after UCP1 inhibition by guanosine 5'-diphosphate (GDP). Results UCP1 expression was higher in tPVAT when compared with iWAT in both NDM and STZ-DM mice. The malondialdehyde concentration was elevated in tPVAT from STZ-DM compared to NDM mice. Glutathione peroxidase and reductase activities, as well as reduced glutathione levels, were not different between tPVAT from NDM and STZ-DM mice but were lower compared to iWAT of STZ-DM mice. OXPHOS capacity of tPVAT was significantly decreased after UCP1 inhibition by GDP in protocol 1. While there were no differences in the OXPHOS capacity between NDM and STZ-DM mice in protocol 1, it was increased in STZ-DM compared to NDM mice in protocol 2. Moreover, complex II- and FAO-linked respiration were elevated in STZ-DM mice under UCP1 inhibition. Conclusions Pharmacological therapies could be targeted to modulate UCP1 activity with a significant impact in the uncoupling of mitochondrial bioenergetics in tPVAT.
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