高脂饮食对孕期小鼠脂肪组织构成和炎症特征的影响

doi:10.3969/j.issn.1674-8115.2024.08.007

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (8): 981-990.doi: 10.3969/j.issn.1674-8115.2024.08.007

高脂饮食对孕期小鼠脂肪组织构成和炎症特征的影响

卢星宇¹(), 徐一丹¹, 刘亦沁¹, 张骞仁², 董艳¹^,³()

^1.上海交通大学医学院附属新华医院内分泌科，上海 200092
^2.上海交通大学医学院附属新华医院消化科，上海 200092
^3.上海市儿科医学研究所，上海 200092

收稿日期:2024-03-12 接受日期:2024-04-07 出版日期:2024-08-28 发布日期:2024-08-27
通讯作者: 董艳 E-mail:luxingyu0912@163.com;dongyansh@sjtu.edu.cn
作者简介:卢星宇（1998—），女，硕士生；电子信箱：luxingyu0912@163.com。
基金资助:
国家重点研发计划(2018YFC1004604);上海市科学技术委员会科研基金资助项目(18ZR1431100)

Effect of high-fat diet on adipose tissues structure and inflammatory characteristics during pregnancy in mice

LU Xingyu¹(), XU Yidan¹, LIU Yiqin¹, ZHANG Qianren², DONG Yan¹^,³()

^1.Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
^2.Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
^3.Shanghai Institute of Pediatrics, Shanghai 200092, China

Received:2024-03-12 Accepted:2024-04-07 Online:2024-08-28 Published:2024-08-27
Contact: DONG Yan E-mail:luxingyu0912@163.com;dongyansh@sjtu.edu.cn
Supported by:
National Key Research and Development Program(2018YFC1004604);Scientific Research Fund of Shanghai Municipal Commission of Science and Technology(18ZR1431100)

摘要/Abstract

摘要：

目的·探究高脂饮食后雌鼠孕前、孕期脂肪组织的改变及其对子代脂肪组织可能产生的影响。方法·C57BL/6J雌性小鼠随机接受普通饮食（CON组，n=12）和高脂饮食（HFD组，n=12）5周；根据是否妊娠再分为普通饮食非妊娠组（CON-UN组）、普通饮食妊娠组（CON-P组）和高脂饮食非妊娠组（HFD-UN组）、高脂饮食妊娠组（HFD-P组）。雌鼠在孕期和哺乳期均维持原有饮食。雌鼠分别于喂饲5周或孕18.5 d取其白色脂肪组织（内脏）和棕色脂肪组织（肩胛）。两组孕鼠的子代断乳后，分别接受普通饮食至第11周，取子代脂肪组织。采用苏木精-伊红（H-E）染色观察脂肪细胞的变化；流式细胞术检测白色脂肪组织中CD4⁺T细胞、CD8⁺T细胞、总T细胞、CD4⁺T细胞/CD8⁺T细胞比值及NK细胞的比例；实时荧光定量聚合酶链反应（RT-PCR）检测白色脂肪组织IL-6和IL-1β mRNA的表达。结果·高脂饮食喂养5周后，HFD组雌鼠体质量高于CON组雌鼠（P<0.05）。高脂饮食后，育龄期雌鼠和妊娠末期雌鼠的白色脂肪和棕色脂肪的质量均显著增加（均P<0.05）。 HFD-UN组和HFD-P组雌鼠白色脂肪组织中同一视野下细胞数量明显减少，脂肪细胞大小不一，脂滴占比增大，细胞体积显著增大；HFD-UN组和HFD-P组脂滴面积占视野总面积的比例分别与CON-UN组和CON-P组比较，差异均有统计学意义（均P<0.05）。HFD-UN组和HFD-P组棕色脂肪细胞则呈现出相对混乱的排列，脂肪细胞大小不一，但细胞体积无明显改变。HFD-UN组和HFD-P组脂肪组织中CD8⁺T细胞比例和总T细胞比例升高，炎症因子IL-6、IL-1β mRNA表达水平升高；分别与CON-UN组和CON-P组比较，差异均具有统计学意义（均P<0.05）。育龄期雌鼠（HFD-UN组）脂肪组织中NK细胞比例降低，但在妊娠期（HFD-P组）NK细胞比例则明显升高，两者呈现相反趋势。HFD组子代断乳后恢复普通饮食，其体质量、白色脂肪和棕色脂肪质量仍显著高于CON组子代（均P<0.05），且白色脂肪细胞体积显著增大。结论·高脂饮食可引起育龄期和妊娠期雌鼠脂肪细胞结构、免疫细胞比例改变及炎症水平升高，并影响子代脂肪组织结构；脂肪组织可能是介导肥胖代际传递的新载体。

关键词: 高脂饮食, 脂肪组织, 妊娠, 母子代际传递

Abstract:

Objective ·To investigate the changes of adipose tissues in mice after high-fat diet before and during pregnancy and the potential effects on adipose tissues in their offspring. Methods ·C57BL/6J female mice were randomly assigned to the normal diet (CON group, n=12) or the high-fat diet (HFD group, n=12) for 5 weeks. The two groups were further subdivided according to pregnancy: a normal diet non-pregnancy group (CON-UN group), a normal diet pregnancy group (CON-P group), a high-fat diet non-pregnancy group (HFD-UN group), and a high-fat diet pregnancy group (HFD-P group). The original diet was maintained during pregnancy and lactation. White adipose tissues (WAT) and brown adipose tissues (BAT) were collected from visceral and scapula of mice after 5 weeks of feeding or E18.5d. Offspring from both dietary groups were placed on a normal diet after weaning, and their adipose tissues were collected at the 11th week. H-E staining was used to observe the changes of adipocytes. Flow cytometry was employed to detect the proportions of CD4⁺T cells, CD8⁺T cells, total T cells, CD4⁺T/CD8⁺T and NK cells in WAT. RT-PCR was used to assess the expression of IL-6 and IL-1β mRNA in WAT. Results ·After 5 weeks on a high-fat diet, the body weight of female mice in the HFD group was higher than that in the CON group (P<0.05). Both WAT and BAT weights were markedly increased in the HFD groups before and during pregnancy (both P<0.05). In the WAT from HFD-UN and HFD-P groups, the number of cells within the same visual field decreased, the size of adipose cells varied, the proportion of fat droplets increased and the cell volume expanded. The proportion of lipid drop area to total visual field in the HFD-UN group and HFD-P group was compared with the CON-UN group and CON-P group, respectively, and the difference was statistically significant (all P<0.05). BAT in the HFD-UN and HFD-P groups showed a relatively chaotic arrangement and varying adipocyte sizes, although cell volume remained unchanged. The proportions of CD8⁺T cells and total T cells in adipose tissues were elevated in the HFD-UN and HFD-P groups, accompanied by increased mRNA levels of IL-6 and IL-1β, respectively, compared with the CON-UN and CON-P groups, and the differences were statistically significant (all P<0.05). NK cells proportions decreased at reproductive age (HFD-UN group) but increased significantly during pregnancy (HFD-P group), showing a divergent trend. Despite a return to a normal diet after weaning, offspring from the high-fat diet group had significantly higher weight of body, WAT and BAT, compared to those of normal diet (all P<0.05), and the volume of WAT was significantly enlarged. Conclusion ·A high-fat diet can induce the changes of adipocyte structure and immune cell ratio, and elevate inflammation levels in adipose tissues before and during pregnancy, which also impacts the adipose structure in offspring. Adipose tissue may be a new vector mediating the intergenerational transmission of obesity.

Key words: high-fat diet, adipose tissue, pregnancy, intergenerational transmission

中图分类号:

R715.3

卢星宇, 徐一丹, 刘亦沁, 张骞仁, 董艳. 高脂饮食对孕期小鼠脂肪组织构成和炎症特征的影响[J]. 上海交通大学学报（医学版）, 2024, 44(8): 981-990.

LU Xingyu, XU Yidan, LIU Yiqin, ZHANG Qianren, DONG Yan. Effect of high-fat diet on adipose tissues structure and inflammatory characteristics during pregnancy in mice[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(8): 981-990.

图/表 6

图1 雌鼠高脂饮食后摄食量、体质量、脂肪组织质量的改变Note： A/B. Weekly food intake (A) and body weight (B) of female mice before mating. C/D. The weight of white adipose tissues (C) and brown adipose tissues (D) in different groups. ①P=0.013; ②P=0.014; ③P=0.000; ④P=0.002; ⑤P=0.012; ⑥P=0.017.

Fig 1 Changes of food intake, body weight, and adipose tissues weight in female mice after high-fat diet

图2 高脂饮食后育龄期和妊娠末期雌鼠白色脂肪组织和棕色脂肪组织结构变化Note： A/B. The structure of white adipose tissues and the proportion of cell area to total area in mice at reproductive age (A) and at the end of pregnancy (B). C/D. The structure of brown adipose tissues and the proportion of cell area to total area in mice at reproductive age (C) and at the end of pregnancy (D). ①P=0.002; ②P=0.000.

Fig 2 Structure of white adipose tissues and brown adipose tissues after high-fat diet in female mice at reproductive age and at the end of pregnancy

图3 高脂饮食后育龄期和妊娠末期雌鼠脂肪组织中T细胞比例变化Note： A. Scatter diagram of T cells in the adipose tissues of female mice at reproductive age. B?E. The proportion of CD4+T cells (B), CD8+T cells (C), T cells (D) and CD4+T cells/CD8+T cells (E) in adipose tissues of female mice at reproductive age. F.Scatter diagram of T cells in the adipose tissues of female mice at the end of pregnancy. G?J. The proportion of CD4+T cells (G), CD8+T cells (H), T cells (I) and CD4+T cells/CD8+T cells (J) in adipose tissues of female mice at the end of pregnancy. ①P=0.000; ②P=0.030; ③P=0.005; ④P=0.019; ⑤P=0.021; ⑥P=0.033.

Fig 3 Changes of T cell proportion in adipose tissues of female mice at reproductive age and at the end of pregnancy after high-fat diet

图4 高脂饮食后育龄期和妊娠末期雌鼠脂肪组织中NK细胞比例变化Note： A/B. Scatter diagram (A) and the proportion (B) of NK cells in the adipose tissues of female mice at reproductive age. C/D. Scatter diagram (C) and the proportion (D) of NK cells in the adipose tissues of female mice at the end of pregnancy. ①P=0.006; ②P=0.022.

Fig 4 Changes of NK cell proportion in adipose tissues of female mice at reproductive age and at the end of pregnancy after high-fat diet

图5 高脂饮食后育龄期和妊娠末期雌鼠脂肪组织中炎症因子表达变化Note： A/B. The mRNA expression levels of IL-6 (A) and IL-1β (B) in the adipose tissues of female mice at reproductive age. C/D. The mRNA expression levels of IL-6 (C) and IL-1β (D) in the adipose tissues of female mice at the end of pregnancy. ①P=0.019; ②P=0.048; ③P=0.018; ④P=0.033.

Fig 5 Expression of inflammatory factors after high-fat diet in adipose tissues of female mice at reproductive age and at the end of pregnancy

图6 母鼠高脂饮食后子代体质量、脂肪组织质量及脂肪组织结构的变化Note： A. The body weight of offspring. B/C.The weight of brown adipose tissues (B) and white adipose tissues (C) of offspring. D. The structure of white adipose tissues and the proportion of cell area to total area in offspring. E. The structure of brown adipose tissues and the proportion of cell area to total area in offspring. ①P=0.012; ②P=0.030; ③P=0.026; ④P=0.035.

Fig 6 Changes of body weight, adipose tissues weight and adipose tissues structure in offspring from high-fat diet mice

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高脂饮食对孕期小鼠脂肪组织构成和炎症特征的影响

Effect of high-fat diet on adipose tissues structure and inflammatory characteristics during pregnancy in mice

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