College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
Poult Sci. 2024 Nov;103(11):104171. doi: 10.1016/j.psj.2024.104171. Epub 2024 Aug 5.
The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 μM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins.
前体脂肪细胞的增生和肥大与动物体内的脂质沉积密切相关。丁酸被报道参与脂质代谢。本研究旨在探讨丁酸对鸡前体脂肪细胞 2 系（ICP2）增殖和分化的影响。ICP2 分别用 12mM 丁酸处理 48 小时进行增殖试验，用 4mM 丁酸加 200μM 油酸处理 3 天进行分化试验。增殖试验中，用 12mM 丁酸处理 48 小时后，2039 个基因显著上调，780 个基因显著下调。同时，丁酸组细胞周期、DNA 复制和 p53 信号通路下调。更重要的是，12mM 丁酸抑制了细胞增殖基因 PCNA、CDK1 和 CDK2 在丁酸组中的表达（P＜0.05），PCNA 和 CDK1 的蛋白表达水平也显著降低（P＜0.05）。油红染色显示，用 4mM 丁酸处理后，ICP2 中红色脂肪滴的存在减少，总胆固醇（TC）和甘油三酯（TG）水平降低。RNA-seq 分析显示，与 OA 组（油酸）相比，OAB 组（油酸+丁酸）中上调和下调的基因数分别为 2095 个和 1042 个。同时，AMPK 信号通路、FOXO 信号通路和黏附斑在 OAB 组中显著富集。此外，4mM 丁酸抑制了 OAB 组中脂肪分化基因 FABP4、C/EBPα、PPARγ和 LPL 的表达（P＜0.05），以及脂肪生成蛋白 FABP4、C/EBP-α和 PPARγ（P＜0.05）。总之，12mM 丁酸通过减缓细胞周期进程有效抑制 ICP2 的增殖，而 4mM 丁酸通过抑制脂质分化标记基因和蛋白的表达减少脂质滴的生成，从而减轻脂质沉积。
