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解析睾酮和二氢睾酮对褐鳟原代肝细胞中脂质代谢基因的影响。

Deciphering influences of testosterone and dihydrotestosterone on lipid metabolism genes using brown trout primary hepatocytes.

机构信息

Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto (U.Porto), Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, P 4450-208 Matosinhos, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (U.Porto), Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto, Portugal.

Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto (U.Porto), Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, P 4450-208 Matosinhos, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (U.Porto), Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto, Portugal.

出版信息

Aquat Toxicol. 2021 Jun;235:105819. doi: 10.1016/j.aquatox.2021.105819. Epub 2021 Mar 26.

Abstract

Despite of physiological and toxicological relevance, the potential of androgens to influence fish lipid metabolism remains poorly explored. Here, brown trout primary hepatocytes were exposed to six concentrations (1 nM to 100 μM) of dihydrotestosterone (DHT) and testosterone (T), to assess changes in the mRNA levels of genes covering diverse lipid metabolic pathways. Acsl1, essential for fatty acid activation, was up-regulated by T and DHT, whereas the lipogenic enzymes FAS and ACC were up-regulated by the highest (100 μM) concentration of T and DHT, respectively. ApoA1, the major component of high-density lipoprotein (HDL), was down-regulated by both androgens. PPARγ, linked to adipogenesis and peroxisomal β-oxidation, was down-regulated by T and DHT, while Acox1-3I, rate-limiting in peroxisomal β-oxidation, was down-regulated by T. Fabp1, StAR and LPL were not altered. Our findings suggest that androgens may impact on lipid transport, adipogenesis and fatty acid β-oxidation and promote lipogenesis in fish liver.

摘要

尽管雄激素具有生理和毒理学相关性,但它们影响鱼类脂质代谢的潜力仍未得到充分探索。在这里,我们将棕鳟原代肝细胞暴露于六种浓度(1 nM 至 100 μM)的二氢睾酮(DHT)和睾酮(T)中,以评估涵盖各种脂质代谢途径的基因的 mRNA 水平变化。脂肪酸激活所必需的 Acsl1 被 T 和 DHT 上调,而 lipogenic 酶 FAS 和 ACC 分别被 T 和 DHT 的最高浓度(100 μM)上调。载脂蛋白 A1 是高密度脂蛋白(HDL)的主要成分,被两种雄激素下调。与脂肪生成和过氧化物酶体β-氧化有关的 PPARγ 被 T 和 DHT 下调,而过氧化物酶体β-氧化的限速酶 Acox1-3I 被 T 下调。Fabp1、StAR 和 LPL 没有改变。我们的研究结果表明,雄激素可能影响鱼类肝脏中的脂质转运、脂肪生成和脂肪酸β-氧化,并促进脂肪生成。

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