Yu Hao, Gao Xinxing, Loor Juan J, Jiang Qianming, Fang Zhiyuan, Hao Xue, Shi Zhen, Fan Minghe, Chen Meng, Li Xinwei, Liu Guowen, Wang Zhe, Li Xiaobing, Du Xiliang
Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Jilin, China.
Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States.
Front Vet Sci. 2022 Feb 8;9:816064. doi: 10.3389/fvets.2022.816064. eCollection 2022.
Excessive lipid mobilization for adipose tissue caused by severe negative energy balance is the pathological basis for subclinical ketosis (SCK) in dairy cows. In non-ruminants, transcription factor EB (TFEB) was reported to play a role in the regulation of lipid catabolism, but its role in the control of lipolysis in the bovine is unknown. The present study aimed to determine whether the enhanced TFEB transcriptional activity contributes to lipolysis of adipose tissue in SCK cows, and to explore the possibility of establishing a therapeutic strategy by using TFEB as a target to control lipolysis. Thirty cows with similar lactation number (media = 3, range = 2-4) and days in milk (media = 6 d, range = 3-9) were selected into a healthy control ( = 15) and SCK ( = 15) group, and used for subcutaneous adipose tissue biopsies and blood sampling. Adipocytes from healthy Holstein calves were used as a model for studies involving treatment with 10 μ isoproterenol (ISO) for 0, 1, 2 and 3 h, 250 n of the TFEB activator Torin1 for 3 h, or used for transfection with TFEB small interfering RNA for 48 h followed by treatment with 10 μ ISO for 3 h. Compared with healthy cows, adipose tissue in SCK cows showed increased lipolysis accompanied by enhanced TFEB transcriptional activity. , ISO and Torin1 treatment increased lipolysis and enhanced TFEB transcriptional activity in calf adipocytes. However, knockdown of attenuated ISO-induced lipolysis in adipocytes. Overall, these findings indicated that enhanced transcriptional activity of TFEB may contribute to lipolysis of adipose tissue in dairy cows with SCK. The regulation of TFEB activity may be an effective therapeutic strategy for controlling overt lipolysis in ketotic cows.
严重负能量平衡导致的来自脂肪组织的过度脂质动员是奶牛亚临床酮病（SCK）的病理基础。在非反刍动物中，据报道转录因子EB（TFEB）在脂质分解代谢的调节中发挥作用，但其在牛脂肪分解控制中的作用尚不清楚。本研究旨在确定增强的TFEB转录活性是否有助于SCK奶牛脂肪组织的脂肪分解，并探索以TFEB为靶点建立控制脂肪分解治疗策略的可能性。选择30头泌乳次数相似（中位数=3，范围=2 - 4）且产奶天数相似（中位数=6天，范围=3 - 9）的奶牛，分为健康对照组（n = 15）和SCK组（n = 15），用于皮下脂肪组织活检和血液采样。来自健康荷斯坦犊牛的脂肪细胞用作模型，进行涉及用10 μM异丙肾上腺素（ISO）处理0、1、2和3小时、用250 nM的TFEB激活剂Torin1处理3小时的研究，或用于用TFEB小干扰RNA转染48小时，随后用10 μM ISO处理3小时。与健康奶牛相比，SCK奶牛脂肪组织的脂肪分解增加，同时TFEB转录活性增强。此外，ISO和Torin1处理增加了犊牛脂肪细胞的脂肪分解并增强了TFEB转录活性。然而，敲低TFEB减弱了ISO诱导的脂肪细胞脂肪分解。总体而言，这些发现表明TFEB转录活性增强可能有助于SCK奶牛脂肪组织的脂肪分解。调节TFEB活性可能是控制酮病奶牛明显脂肪分解的有效治疗策略。
