Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro.
Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro.
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DOI：
10.1177/1479164118757924
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发表时间：
2018-05
影响因子：
2.4
通讯作者：
Pirmohamed M
中科院分区：
文献类型：
--
作者：
Pushpakom SP;Adaikalakoteswari A;Owen A;Back DJ;Tripathi G;Kumar S;McTernan P;Pirmohamed M
HIV阳性患者的抗逆转录病毒治疗导致胰岛素抵抗，这是该患者群体中观察到的各种代谢异常和心血管疾病的发病机制的核心。我们研究了替米沙坦（一种抗高血压药）对体外脂肪细胞的剂量-反应关系，以确定其是否具有代谢有益作用。使用体外慢性毒性模型（3 T3-F442 A小鼠和原代人脂肪细胞），我们分别使用脂质蓄积试验和实时聚合酶链反应评价了不同浓度的替米沙坦对脂肪细胞分化和成脂基因表达的影响。脂肪因子分泌和胰岛素信号介质的表达进行了评价，使用酶联免疫吸附试验。替米沙坦可部分逆转抗逆转录病毒药物对脂肪细胞脂质蓄积、脂肪形成调节因子（过氧化物酶体增殖物受体-γ和lipin 1）表达、脂肪因子分泌和胰岛素信号传导介质pAktSer 473表达的有害作用。替米沙坦的代谢效应遵循非单调反应，在原代人脂肪细胞模型中5 µM时观察到最大效应。替米沙坦在体外脂肪细胞中具有有益的代谢作用，但其减少HIV感染个体中抗逆转录病毒诱导的心脏代谢疾病的潜力需要在设计良好、具有充分把握度的临床试验中进行评估。
Antiretroviral therapy in HIV-positive patients leads to insulin resistance which is central to the pathogenesis of various metabolic abnormalities and cardiovascular disease seen in this patient group. We have investigated the dose–response relationship of telmisartan, an antihypertensive, on adipocytes in vitro in order to determine whether it may have metabolic beneficial effects. Using in vitro chronic toxicity models (3T3-F442A murine and primary human adipocytes), we evaluated the effects of different concentrations of telmisartan on adipocyte differentiation and adipogenic gene expression using lipid accumulation assays and real-time polymerase chain reaction, respectively. Adipokine secretion and expression of insulin signalling mediators were evaluated using enzyme-linked immunosorbent assays. Telmisartan partially reversed the deleterious effects of antiretrovirals on adipocyte lipid accumulation, expression of adipogenic regulators (peroxisome proliferator receptor-gamma and lipin 1), adipokine secretion and expression of the insulin signalling mediator pAktSer473. The metabolic effects of telmisartan followed a non-monotonic response with the maximal effect observed at 5 µM in the primary human adipocyte model. Telmisartan has beneficial metabolic effects in adipocytes in vitro, but its potential to reduce antiretroviral-induced cardiometabolic disease in HIV-infected individuals needs to be evaluated in a well-designed adequately powered clinical trial.
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影响因子：
158.5
作者：
Nissen, Steven E.;Wolski, Kathy
通讯作者：
Wolski, Kathy
DOI：
10.1042/bj20121598
发表时间：
2013-07-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Kim HE;Bae E;Jeong DY;Kim MJ;Jin WJ;Park SW;Han GS;Carman GM;Koh E;Kim KS
通讯作者：
Kim KS
影响因子：
5.8
作者：
Barb, D;Wadhwa, SG;Mantzoros, CS
通讯作者：
Mantzoros, CS
影响因子：
3.8
作者：
Lee, Grace A.;Rao, Madhu;Grunfeld, Carl
通讯作者：
Grunfeld, Carl
影响因子：
5.4
作者：
Arama, V.;Munteanu, D. I.;Arama, S. S.
通讯作者：
Arama, S. S.