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围产期奶牛皮下脂肪组织中内源性大麻素系统的特征及其与代谢谱的关系。

Characterization of the endocannabinoid system in subcutaneous adipose tissue in periparturient dairy cows and its association to metabolic profiles.

机构信息

Department of Ruminant Science, Institute of Animal Sciences, Volcani Center, Rishon Lezion, Israel.

The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

出版信息

PLoS One. 2018 Nov 7;13(11):e0205996. doi: 10.1371/journal.pone.0205996. eCollection 2018.

Abstract

Adipose tissue (AT) plays a major role in metabolic adaptations in postpartum (PP) dairy cows. The endocannabinoid (eCB) system is a key regulator of metabolism and energy homeostasis; however, information about this system in ruminants is scarce. Therefore, this work aimed to assess the eCB system in subcutaneous AT, and to determine its relation to the metabolic profile in peripartum cows. Biopsies of AT were performed at 14 d prepartum, and 4 and 30 d PP from 18 multiparous peripartum cows. Cows were categorized retrospectively according to those with high body weight (BW) loss (HWL, 8.5 ± 1.7% BW loss) or low body weight loss (LWL, 2.9 ± 2.5% BW loss) during the first month PP. The HWL had higher plasma non-esterified fatty acids and a lower insulin/glucagon ratio PP than did LWL. Two-fold elevated AT levels of the main eCBs, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), were found 4 d PP compared with prepartum in HWL, but not in LWL cows. AT levels of the eCB-like molecules oleoylethanolamide, palmitoylethanolamide, and of arachidonic acid were elevated PP compared with prepartum in all cows. The abundance of monoglyceride lipase (MGLL), the 2-AG degrading enzyme, was lower in HWL vs. LWL AT PP. The relative gene expression of the cannabinoid receptors CNR1 and CNR2 in AT tended to be higher in HWL vs. LWL PP. Proteomic analysis of AT showed an enrichment of the inflammatory pathways' acute phase signaling and complement system in HWL vs. LWL cows PP. In summary, eCB levels in AT were elevated at the onset of lactation as part of the metabolic adaptations in PP dairy cows. Furthermore, activating the eCB system in AT is most likely associated with a metabolic response of greater BW loss, lipolysis, and AT inflammation in PP dairy cows.

摘要

脂肪组织(AT)在产后奶牛的代谢适应中起着重要作用。内源性大麻素(eCB)系统是代谢和能量平衡的关键调节剂;然而,反刍动物中关于该系统的信息很少。因此,本工作旨在评估产后奶牛皮下 AT 中的 eCB 系统,并确定其与围产期奶牛代谢特征的关系。在产前 14 天、产后 4 天和 30 天,从 18 头经产围产期奶牛中采集 AT 活检。根据产后第一个月体重损失(BW 损失)较高(HWL,8.5±1.7% BW 损失)或体重损失较低(LWL,2.9±2.5% BW 损失),对奶牛进行回顾性分类。与 LWL 相比,HWL 产后的血浆非酯化脂肪酸更高,胰岛素/胰高血糖素比值更低。与产前相比,HWL 产后 4 天 AT 中主要 eCBs 的水平升高了两倍,即 N-花生四烯酸乙醇胺(AEA)和 2-花生四烯酸甘油(2-AG),而 LWL 奶牛中则没有。与产前相比,所有奶牛产后 AT 中的 eCB 样分子油酸乙醇酰胺、棕榈酸乙醇酰胺和花生四烯酸的水平均升高。与 LWL 相比,HWL 产后 AT 中的单酰基甘油脂肪酶(MGLL),即 2-AG 降解酶的丰度较低。产后 AT 中大麻素受体 CNR1 和 CNR2 的相对基因表达在 HWL 中趋于高于 LWL。AT 的蛋白质组分析表明,HWL 中炎症途径的急性期信号和补体系统较 LWL 更为丰富。总之,eCB 水平在产后泌乳期开始时升高,是围产期奶牛代谢适应的一部分。此外,在产后奶牛中,AT 中 eCB 系统的激活很可能与更大的 BW 损失、脂肪分解和 AT 炎症的代谢反应有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d8/6221292/53826fcd3e5d/pone.0205996.g001.jpg

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