Oxylipin responses to fasting and insulin infusion in a large mammalian model of fasting-induced insulin resistance, the northern elephant seal.
Oxylipin responses to fasting and insulin infusion in a large mammalian model of fasting-induced insulin resistance, the northern elephant seal.
复制标题
在禁食引起的胰岛素抵抗的大型哺乳动物模型——北象海豹中，氧脂素对禁食和胰岛素输注的反应。
DOI：
10.1152/ajpregu.00016.2021
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Ortiz,RudyM
中科院分区：
文献类型：
--
作者：
Wright,DanaN;Katundu,KondwaniGH;Viscarra,JoseA;Crocker,DanielE;Newman,JohnW;LaFrano,MichaelR;Ortiz,RudyM
北象海豹 (Mirounga angustirostris) 幼崽断奶后长时间禁食的特点是依赖脂质代谢和可逆的禁食诱导的胰岛素抵抗，为检查胰岛素对脂质代谢的影响提供了一个独特的模型。我们之前已经表明，急性胰岛素输注会导致脂肪酸代谢发生变化，具体取决于禁食时间。这项研究通过检查禁食时间和胰岛素输注对氧脂质（源自多不饱和脂肪酸氧化的生物活性代谢物）循环水平的影响来补充之前的研究。对北象海豹幼崽进行了两个断奶后阶段的研究（n=5/期）：早期禁食（断奶后 1-2 周；127±1kg）和晚期禁食（断奶后 6-7 周；93±4kg）。对不同组的幼犬进行称重、镇静并注射 65 mU/kg 的胰岛素。在输注前(T0)以及输注后10、30、60和120分钟收集血浆。通过 UPLC-ESI-MS/MS 分析了约 80 种氧脂质的概况。九种氧脂素在禁食早期和晚期之间发生变化，八种氧脂质因胰岛素输注而改变。在 T0 样本中，禁食降低了前列腺素 F2α (PGF2α)，并增加了 14,15-二羟基二十碳三烯酸 (14,15-DiHETrE)、20-羟基二十碳四烯酸 (20-HETE) 和 4-羟基二十二碳六烯酸 (4-HDoHE) (P< 0.03)，而胰岛素输注导致了这些相同代谢物的曲线下面积 (AUC) 水平 (P< 0.05)。此外，12-12-氢过氧二十碳四烯酸（HpETE）和12-HETE分别随着禁食和胰岛素输注而降低（P<0.04）。禁食期间和响应胰岛素输注而改变的氧脂质可能导致胰岛素抵抗的表现并参与相关细胞过程的代谢调节。
The prolonged, postweaning fast of northern elephant seal (Mirounga angustirostris) pups is characterized by a reliance on lipid metabolism and reversible, fasting-induced insulin resistance, providing a unique model to examine the effects of insulin on lipid metabolism. We have previously shown that acute insulin infusion induced a shift in fatty acid metabolism dependent on fasting duration. This study complements the previous study by examining the effects of fasting duration and insulin infusion on circulating levels of oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids. Northern elephant seal pups were studied at two postweaning periods (n= 5/period): early fasting (1–2 wk postweaning; 127 ± 1 kg) and late fasting (6–7 wk postweaning; 93 ± 4 kg). Different cohorts of pups were weighed, sedated, and infused with 65 mU/kg of insulin. Plasma was collected prior to infusion (T0) and at 10, 30, 60, and 120 min postinfusion. A profile of ∼80 oxylipins was analyzed by UPLC-ESI-MS/MS. Nine oxylipins changed between early and late fasting and eight were altered in response to insulin infusion. Fasting decreased prostaglandin F2α (PGF2α) and increased 14,15-dihydroxyicosatrienoic acid (14,15-DiHETrE), 20-hydroxyeicosatetraenoic acid (20-HETE), and 4-hydroxy-docosahexaenoic acid (4-HDoHE) (P< 0.03) in T0 samples, whereas insulin infusion resulted in an inverse change in area-under-the-curve (AUC) levels in these same metabolites (P< 0.05). In addition, 12-12-hydroperoxyeicosatetraenoic acid (HpETE) and 12-HETE decreased with fasting and insulin infusion, respectively (P< 0.04). The oxylipins altered during fasting and in response to insulin infusion may contribute to the manifestation of insulin resistance and participate in the metabolic regulation of associated cellular processes.