Department of Biological Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Bamfield Marine Sciences Centre, Bamfield, BC V0R 1B0, Canada.
Department of Biological Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Bamfield Marine Sciences Centre, Bamfield, BC V0R 1B0, Canada.
Gen Comp Endocrinol. 2024 Jun 1;352:114514. doi: 10.1016/j.ygcen.2024.114514. Epub 2024 Apr 4.
Hormonal influence on hepatic function is a critical aspect of whole-body energy balance in vertebrates. Catecholamines and corticosteroids both influence hepatic energy balance via metabolite mobilization through glycogenolysis and gluconeogenesis. Elasmobranchs have a metabolic organization that appears to prioritize the mobilization of hepatic lipid as ketone bodies (e.g. 3-hydroxybutyrate [3-HB]), which adds complexity in determining the hormonal impact on hepatic energy balance in this taxon. Here, a liver perfusion was used to investigate catecholamine (epinephrine [E]) and corticosteroid (corticosterone [B] and 11-deoxycorticosterone [DOC]) effects on the regulation of hepatic glucose and 3-HB balance in the North Pacific Spiny dogfish, Squalus suckleyi. Further, hepatic enzyme activity involved in ketogenesis (3-hydroxybutyrate dehydrogenase), glycogenolysis (glycogen phosphorylase), and gluconeogenesis (phosphoenolpyruvate carboxykinase) were assessed in perfused liver tissue following hormonal application to discern effects on hepatic energy flux. mRNA transcript abundance key transporters of glucose (glut1 and glut4) and ketones (mct1 and mct2) and glucocorticoid function (gr, pepck, fkbp5, and 11βhsd2) were also measured to investigate putative cellular components involved in hepatic responses. There were no changes in the arterial-venous difference of either metabolite in all hormone perfusions. However, perfusion with DOC increased gr transcript abundance and decreased flow rate of perfusions, suggesting a regulatory role for this corticosteroid. Phosphoenolpyruvate carboxykinase activity increased following all hormone treatments, which may suggest gluconeogenic function; E also increased 3-hydroxybutyrate dehydrogenase activity, suggesting a function in ketogenesis, and decreased pepck and fkbp5 transcript abundance, potentially showing some metabolic regulation. Overall, we demonstrate hormonal control of hepatic energy balance using liver perfusions at various levels of biological organization in an elasmobranch.
激素对肝功能的影响是脊椎动物全身能量平衡的一个关键方面。儿茶酚胺和皮质类固醇都通过糖原分解和糖异生来影响肝能量平衡,从而使代谢物动员。软骨鱼类的代谢组织似乎优先动员肝脂质作为酮体(例如 3-羟丁酸[3-HB]),这增加了确定该分类群中激素对肝能量平衡影响的复杂性。在这里,使用肝灌注来研究儿茶酚胺(肾上腺素[E])和皮质类固醇(皮质酮[B]和 11-脱氧皮质酮[DOC])对北太平洋刺鲨,Squalus suckleyi 肝葡萄糖和 3-HB 平衡的调节作用。此外,在应用激素后,评估灌注肝组织中与酮生成(3-羟丁酸脱氢酶)、糖原分解(糖原磷酸化酶)和糖异生(磷酸烯醇丙酮酸羧激酶)相关的肝酶活性,以辨别对肝能量通量的影响。还测量了葡萄糖(glut1 和 glut4)和酮(mct1 和 mct2)的关键转运体以及糖皮质激素功能(gr、pepck、fkbp5 和 11βhsd2)的 mRNA 转录丰度,以研究肝反应中涉及的潜在细胞成分。在所有激素灌注中,两种代谢物的动静脉差都没有变化。然而,DOC 灌注增加了 gr 转录丰度并降低了灌注流量,表明这种皮质类固醇具有调节作用。所有激素处理后磷酸烯醇丙酮酸羧激酶活性增加,这可能表明具有糖异生功能;E 还增加了 3-羟丁酸脱氢酶活性,表明其具有酮生成功能,并降低了 pepck 和 fkbp5 的转录丰度,可能表现出一些代谢调节。总的来说,我们在软骨鱼类的不同生物学组织水平上使用肝灌注证明了激素对肝能量平衡的控制。