FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling.
FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling.
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FGF21 通过 AMPK 信号传导增强脂质氧化和减少脂肪生成，从而减少牛肝细胞中的脂质积累
DOI：
10.3390/ani12070939
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发表时间：
2022-04-06
期刊：
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Kong Y;Zhao C;Tan P;Liu S;Huang Y;Zeng F;Ma P;Guo Y;Zhao B;Wang J
奶牛围产期能量摄入减少和需求增加引起的能量负平衡（NEB）导致脂质动员，导致非酯化脂肪酸（NEFA）在肝脏中积累。NEFA是减少甘油三酯（TG）酯化合成的底物，导致能量代谢紊乱，如酮症和脂肪肝。成纤维细胞生长因子21（FGF 21）治疗可使奶牛肝脏中的TG含量降低50%。本研究进一步发现FGF 21通过AMPK信号通路调节牛肝细胞的脂质代谢。SREBF 1、过氧化物酶体增殖物激活受体α（PPARA）及其靶基因的表达发生变化。这对脂质形成、增强脂质氧化和增加脂质转运具有负面影响。提示FGF 21在缓解奶牛围产期代谢性疾病方面可能具有潜在价值，具体的体内研究有待进一步深入。摘要奶牛在围产期由于能量负平衡导致血浆中非酯化脂肪酸（NEFA）含量增加，从而产生剧烈的代谢应激。成纤维细胞生长因子21（FGF 21）是一种肝细胞因子，其激活AMP活化的蛋白激酶（AMPK）信号通路，通过促进catalysts和抑制合成代谢调节来维持细胞内能量平衡和组织完整性。FGF 21处理导致奶牛肝脏中甘油三酯（TG）含量降低50%。然而，尚不清楚FGF 21是否调节牛肝脏中的脂质代谢。本研究的目的是评估FGF 21通过AMPK信号转导对牛肝细胞中脂质代谢的影响。用不同浓度的FGF 21处理从小牛分离的肝细胞或用AMPK抑制剂（BML-275）共处理肝细胞。在此，该研究表明，FGF 21以剂量-反应方式显著降低TG含量，并通过上调参与极低密度脂蛋白（VLDL）分泌的蛋白质（ApoB 100、ApoE和MTTP）促进VLDL分泌。另外，与脂质转运（LDLR和CD 36）和脂质氧化（PPARGC 1A，ACOX 1和CPT 1A）相关的基因在FGF 21处理后上调。此外，FGF 21处理通过SREBF 1、ACACA、FGF 21和ACLY抑制来抑制脂肪生成。在与AMPK抑制剂共同处理后，FGF 21诱导的变化在一些基因中被逆转。总之，这些结果表明，FGF 21适应性地调节能量代谢，对脂肪生成产生负面影响，加强脂质氧化，并通过AMPK信号转导抑制牛肝细胞中的脂质转运。提示FGF 21在缓解奶牛围产期代谢性疾病方面可能具有潜在价值，具体的体内研究有待进一步深入。
Simple Summary The negative energy balance (NEB) caused by decreased energy intake and increased demand during the perinatal period of dairy cows causes lipid mobilization, which leads to the accumulation of non-esterified fatty acids (NEFAs) in the liver. NEFAs are substrates that reduce triglyceride (TG) esterification synthesis, leading to energy metabolic disorders such as ketosis and fatty liver. Fibroblast growth factor 21 (FGF21) treatment can reduce TG content in the liver of dairy cows by 50%. This study further found that FGF21 regulated lipid metabolism in bovine liver cells through the AMPK signaling pathway. The expressions of SREBF1, the peroxisome proliferator-activated receptor α (PPARA) and their target genes were changed. This had a negative effect on lipid formation, enhanced lipid oxidation, and increased lipid transport. The present data suggest the possibility that FGF21 has potential value in alleviating perinatal metabolic diseases in dairy cows, and specific research in vivo should be studied in more detail. Abstract During the periparturient period, dairy cows suffer drastic metabolic stress because of plasma increased non-esterified fatty acids (NEFAs) that stem from a negative energy balance. Fibroblast growth factor 21 (FGF21) is a hepatokine that activates the AMP-activated protein kinase (AMPK) signaling pathway to maintain intracellular energy balance and tissue integrity via the promotion of catabolism and the inhibition of anabolic regulation. FGF21 treatment caused a 50% reduction in triglyceride (TG) content in liver in dairy cows. However, it is not clear whether FGF21 regulates lipid metabolism in bovine liver. The purpose of this study was to evaluate the influence of FGF21 on lipid metabolism via AMPK signaling in bovine hepatocytes. The hepatocytes isolated from calves were treated with different concentrations of FGF21 or co-treated with AMPK inhibitor (BML-275). Herein, the study showed that FGF21 significantly reduced TG content in a dose–response manner and promoted very-low-density lipoprotein (VLDL) secretion via an up-regulation of the proteins (ApoB 100, ApoE and MTTP) involved in VLDL secretion. Otherwise, the genes associated with lipid transport (LDLR and CD36) and lipid oxidation (PPARGC1A, ACOX1 and CPT1A), were up-regulated following FGF21 treatment. Moreover, FGF21 treatment inhibited lipogenesis via SREBF1, ACACA, FASN and ACLY inhibition. After being co-treated with the AMPK inhibitor, FGF21-induced changes were reversed in some genes. In conclusion, these results indicate that FGF21 adaptively regulates energy metabolism for a negative impact on lipogenesis, strengthens lipid oxidation, and inhibited lipid transportation via AMPK signaling in bovine hepatocytes. The present data suggest the possibility that FGF21 has potential value in alleviating perinatal metabolic diseases in dairy cows, and specific research in vivo should be studied in more detail.
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影响因子：
4.1
作者：
Koerner, Cari M.;Roberts, Benjamin S.;Neher, Saskia B.
通讯作者：
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影响因子：
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DOI：
10.1152/ajpregu.00197.2017
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2017-11-01
影响因子：
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3.5
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作者：
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