Adropin: An endocrine link between the biological clock and cholesterol homeostasis.
Adropin: An endocrine link between the biological clock and cholesterol homeostasis.
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DOI：
10.1016/j.molmet.2017.12.002
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发表时间：
2018-03
影响因子：
8.1
通讯作者：
Butler AA
中科院分区：
文献类型：
--
作者：
Ghoshal S;Stevens JR;Billon C;Girardet C;Sitaula S;Leon AS;Rao DC;Skinner JS;Rankinen T;Bouchard C;Nuñez MV;Stanhope KL;Howatt DA;Daugherty A;Zhang J;Schuelke M;Weiss EP;Coffey AR;Bennett BJ;Sethupathy P;Burris TP;Havel PJ;Butler AA
确定血浆肾上腺素浓度的决定因素，肾上腺素是一种从能量平衡相关(ENHO)基因翻译而来的分泌肽，与代谢控制和血管功能有关。在人类隔夜禁食后获得的血浆中，评估了血浆肾上腺素浓度、人口学特征(性别、年龄、体重指数)和循环中的脂肪和葡萄糖代谢生物标记物之间的关系。然后在硅胶、培养的人类细胞和动物模型中评估肾上腺素表达的调节。在人类中，男性的血浆肾上腺素浓度与致动脉粥样硬化的低密度脂蛋白-胆固醇(LDL-C)水平呈负相关(n=349)，而女性则没有(n=0.401)。对雄性小鼠肝脏Enho表达的分析表明，这是由生物钟控制的。表达是有节奏的，在黑暗中最大限度地食用食物时达到顶峰，与RoRα/γ的转录激活相关。光相的最低点与休止期一致，并受到REV-ERB的抑制。非人灵长类动物(恒河猴)的血浆肾上腺素浓度也表现出与摄食时间(07：00和15：00)一致的峰值。RoR反向激动剂SR1001和7-氧合甾醇7-β-羟基甾醇和7-酮胆固醇或REV-ERB激动剂SR9009可抑制培养的人肝癌细胞ENHO的表达。高胆固醇饮食的摄入抑制了肾上腺素转录本在小鼠肝脏中的表达。然而，阿托品的过度表达并不能防止高胆固醇饮食和/或低密度脂蛋白受体突变引起的高胆固醇血症。在人类中，血浆肾上腺素浓度和低密度脂蛋白-C之间的关联表明与肝脂代谢有关。小鼠的研究表明，肾上腺素和胆固醇代谢之间的关系是单向的，主要涉及胆固醇和7-氧合甾醇抑制肾上腺素的表达。通过RoRα/γ配体结合域对脂肪酸、胆固醇和氧固醇的检测表明，肾上腺素表达和细胞脂质代谢之间存在看似合理的功能联系。此外，核受体RoR-α/γ和REV-ERB可能将肾上腺素的合成与碳水化合物和脂肪代谢的昼夜节律结合在一起。在男性中，血浆肾上腺素浓度与低密度循环胆固醇(LDL-C)水平呈负相关。Adropin的表达受生物时钟的核心元件(RORA/G，Rev-Erb)调控。通过ROR配体结合域的类固醇感知在肾上腺素的表达和脂类代谢之间提供了一个合理的联系。在小鼠肝脏中，肾上腺素的表达是有节律性的，并受到外源(饮食)胆固醇的抑制。
Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models. In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis of hepatic Enho expression in male mice suggests control by the biological clock. Expression is rhythmic, peaking during maximal food consumption in the dark correlating with transcriptional activation by RORα/γ. The nadir in the light phase coincides with the rest phase and repression by Rev-erb. Plasma adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001 and the 7-oxygenated sterols 7-β-hydroxysterol and 7-ketocholesterol, or the Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells. Consumption of high-cholesterol diets suppress expression of the adropin transcript in mouse liver. However, adropin over expression does not prevent hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor mutations. In humans, associations between plasma adropin concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse studies suggest that the relationship between adropin and cholesterol metabolism is unidirectional, and predominantly involves suppression of adropin expression by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and oxysterols by the RORα/γ ligand-binding domain suggests a plausible functional link between adropin expression and cellular lipid metabolism. Furthermore, the nuclear receptors RORα/γ and Rev-erb may couple adropin synthesis with circadian rhythms in carbohydrate and lipid metabolism. In male humans, plasma adropin concentrations are inversely related to low-density circulating cholesterol (LDL-C) levels. Adropin expression is regulated by core elements of the biological clock (RORA/G, Rev-Erb). Sterol-sensing by the ROR ligand-binding domain provides a plausible link between adropin expression and lipid metabolism. In mouse liver, adropin expression is rhythmic and suppressed by exogenous (dietary) cholesterol.
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影响因子：
29
作者：
Kumar KG;Trevaskis JL;Lam DD;Sutton GM;Koza RA;Chouljenko VN;Kousoulas KG;Rogers PM;Kesterson RA;Thearle M;Ferrante AW Jr;Mynatt RL;Burris TP;Dong JZ;Halem HA;Culler MD;Heisler LK;Stephens JM;Butler AA
通讯作者：
Butler AA
影响因子：
2.5
作者：
Churchill, Gary A.;Gatti, Daniel M.;Munger, Steven C.;Svenson, Karen L.
通讯作者：
Svenson, Karen L.
小儿阻塞性睡眠呼吸暂停中循环的adropin浓度：与内皮功能的潜在相关性。
DOI：
10.1016/j.jpeds.2013.05.040
发表时间：
2013-10
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Gozal D;Kheirandish-Gozal L;Bhattacharjee R;Molero-Ramirez H;Tan HL;Bandla HP
通讯作者：
Bandla HP
影响因子：
4.9
作者：
Kheirandish-Gozal, L.;Gileles-Hillel, A.;Alonso-Alvarez, M. L.;Peris, E.;Bhattacharjee, R.;Teran-Santos, J.;Duran-Cantolla, J.;Gozal, D.
通讯作者：
Gozal, D.
DOI：
10.4149/bll_2016_020
发表时间：
2016-01-01
影响因子：
1.5
作者：
Akcilar, R.;Kocak, F. E.;Kokdasgil, H.
通讯作者：
Kokdasgil, H.