Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.

中文翻译：

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膳食脂肪补充剂通过 AMPK 介导的猪线粒体稳态缓解低温引起的能量应激

寒冷应激对哺乳动物的生长和健康产生负面影响，已成为制约高纬度和高原畜牧业发展的因素。肠肝轴是能量代谢的核心，但它在低温下调节宿主能量代谢的机制很少被阐明。在本研究中，我们基于肠肝轴评估了猪的糖脂代谢和氧化应激状态，并提出AMP激活蛋白激酶（AMPK）是通过膳食脂肪补充缓解寒冷温度下能量应激的关键靶标。膳食脂肪补充剂减轻了寒冷气温对生长性能和消化酶的负面影响，同时也恢复了荷尔蒙稳态。此外，寒冷的温度暴露增加了空肠中的葡萄糖转运。相反，我们观察到脂质代谢异常，其特征是回肠和血浆中胆汁酸的积累。此外，回肠代谢组学分析结果与空肠能量代谢测量结果一致，膳食脂肪补充增加了线粒体呼吸链和脂质代谢的活性。肝脏作为能量代谢的中枢，其糖脂代谢和氧化应激状态与小肠不一致。具体来说，我们发现寒冷的温度暴露增加了肝脏中的葡萄糖转运，这充分验证了激素可以作用于肝脏来调节葡萄糖输出的想法。此外，膳食脂肪补充抑制了葡萄糖转运和糖酵解，但增加了糖异生、胆汁酸循环和脂质代谢。 AMPK（一种能量受体和调节剂）的持续激活会导致肝脏氧化应激和细胞凋亡；膳食脂肪补充剂通过减少 AMPK 磷酸化来缓解能量压力。冷应激降低了猪的生长性能，加剧了糖脂代谢紊乱和氧化应激损伤。膳食脂肪补充剂通过 AMPK 介导的线粒体稳态改善了生长性能并缓解了低温引起的能量应激。在这项研究中，我们强调了 AMPK 在膳食脂肪补充介导的缓解宿主能量应激以应对环境变化方面的重要性。