The fungal isolate myriocin inhibits serine palmitoyltransferase and de novo ceramide synthesis in rodents; however, the effects of myriocin on ceramide concentrations and metabolism have not been previously investigated in ruminants. In our study, 12 non-lactating crossbred ewes received an intravenous bolus of myriocin (0, 0.1, 0.3, or 1.0 mg/kg/body weight [BW]; CON, LOW, MOD, or HIGH) every 48 h for 17 d. Ewes consumed a high-energy diet from day 1 to 14 and were nutrient-restricted (straw only) from day 15 to 17. Blood was collected preprandial and at 1, 6, and 12 h relative to bolus and nutrient restriction. Tissues were collected following euthanasia on day 17. Plasma was analyzed for free fatty acids (FFAs), glucose, and insulin. Plasma and tissue ceramides were quantified using mass spectrometry. HIGH selectively decreased metabolizable energy intake, BW, and plasma insulin, and increased plasma FFA (Dose, P < 0.05). Myriocin linearly decreased plasma very-long-chain (VLC) ceramide and dihydroceramide (DHCer) by day 13 (Linear, P < 0.05). During nutrient restriction, fold-change in FFA was lower with increasing dose (P < 0.05). Nutrient restriction increased plasma C16:0-Cer, an effect suppressed by MOD and HIGH (Dose × Time, P < 0.05). Myriocin linearly decreased most ceramide and DHCer species in the liver and omental and mesenteric adipose, VLC ceramide and DHCer in the pancreas, and C18:0-Cer in skeletal muscle and subcutaneous adipose tissue (Linear, P ≤ 0.05). We conclude that the intravenous delivery of 0.3 mg of myriocin/kg of BW/48 h decreases circulating and tissue ceramide without modifying energy intake in ruminants.

中文翻译：

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myriocin抑制丝氨酸棕榈酰转移酶对自由采食和限养母羊的影响

真菌分离物多球菌素可抑制啮齿动物的丝氨酸棕榈酰转移酶和神经酰胺从头合成；然而，之前尚未在反刍动物中研究多球菌素对神经酰胺浓度和代谢的影响。在我们的研究中，12 只非哺乳期杂交母羊每 48 小时接受一次静脉推注多球菌素（0、0.1、0.3 或 1.0 mg/kg/体重 [BW]；CON、LOW、MOD 或 HIGH），持续 17 天. 母羊从第 1 天到第 14 天食用高能量饮食，并从第 15 天到第 17 天限制营养（仅吸管）。相对于推注和营养限制，在餐前和 1、6 和 12 小时收集血液。在第 17 天安乐死后收集组织。分析血浆中的游离脂肪酸 (FFA)、葡萄糖和胰岛素。使用质谱法对血浆和组织神经酰胺进行量化。HIGH 选择性地降低可代谢能量摄入、体重和血浆胰岛素，并增加血浆 FFA（剂量，P < 0.05）。到第 13 天，Myriocin 线性降低血浆超长链 (VLC) 神经酰胺和二氢神经酰胺 (DHCer)（线性，P < 0.05）。在营养限制期间，FFA 的倍数变化随着剂量的增加而降低（P < 0.05）。营养限制增加了血浆 C16:0-Cer，这是 MOD 和 HIGH 抑制的效果（剂量 × 时间，P < 0.05）。Myriocin 线性减少肝脏和网膜脂肪和肠系膜脂肪中的大多数神经酰胺和 DHCer，胰腺中的 VLC 神经酰胺和 DHCer，以及骨骼肌和皮下脂肪组织中的 C18:0-Cer（线性，P ≤ 0.05）。我们得出结论，静脉内给药为 0。