高脂饮食对围绝经期脂肪性肝病小鼠肝脏脂质代谢的影响

ZHANG  Wei1; 2; SHI  Jingjing2; 3; WANG  Shan2; 4; WANG  Yayun5; WANG  Song6; LI  Shuo7; QIN  Lihua8*; ZHAO  Linhua2*

doi:10.16098/j.issn.0529-1356.2026.01.016

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解剖学报 ›› 2026, Vol. 57 ›› Issue (1) : 105-115. DOI: 10.16098/j.issn.0529-1356.2026.01.016

组织学胚胎学发育生物学

高脂饮食对围绝经期脂肪性肝病小鼠肝脏脂质代谢的影响

张伟^1,2石晶晶^2,3王杉^2,4王亚运⁵王松⁶李硕⁷秦丽华^8*赵林华^2*

作者信息 +

High-fat diet inducing hepatic lipid metabolism disorder in perimenopausal fatty liver disease mice

ZHANG Wei^1,2, SHI Jing-jing^2,3, WANG Shan^2,4, WANG Ya-yun⁵, WANG Song⁶, LI Shuo⁷, QIN Li-hua^8*, ZHAO Lin-hua^2*

Author information +

文章历史 +

摘要

目的采用双侧卵巢切除（OVX）建立围绝经期脂肪性肝病（PMFLD）小鼠模型，并观察高脂饮食（HFD）对该模型的影响，以探讨其发病机制。方法将24只12周龄C57BL/6J雌性小鼠OVX术后2周随机分成假手术（sham）+维持饲料（ND）组、OVX+ND组、sham+HFD组和OVX+HFD组，每组6只，于第4周对各组小鼠进行各项指标评估。结果 OVX+ND组体重增加值、内脏白色脂肪组织（vWAT）重量及其重量与体重占比，腹股沟白色脂肪组织（iWAT）重量及其重量与体重占比明显高于sham+ND组，肝脏油红O染色比率增加，肝脏谷草转氨酶（AST）和谷丙转氨酶（ALT）水平升高，视野范围内vWAT脂滴数量明显降低，提示PMFLD模型构建成功。肝靶向脂质组检测发现，仅3种磷脂酰胆碱（PC）在各组中有差异，OVX+ND组和OVX+HFD组的PC水平均高于sham+ND组（P<0.05）。与sham+ND组比较，OVX+ND组、sham+HFD组、OVX+HFD组葡萄糖耐量实验（OGTT）的曲线下面积（AUC）均明显增加（P<0.05）。OVX+HFD组OGTT的AUC均高于OVX+ND组、sham+HFD组（P<0.05）。Sham+HFD组胰岛素释放实验（IRT）的AUC均高于sham+ND组、OVX+ND组、OVX+HFD组（P<0.05）。OVX+HFD组IRT的AUC高于OVX+ND组，但是低于sham+HFD组（P<0.05）。OVX+ND组、sham+HFD组、OVX+HFD组中的脂肪酸结合蛋白1型（FABP1）、磷脂转运蛋白（PLTP）表达水平均高于sham+ND组，过氧化物酶体增殖物激活受体（PPARα）表达水平低于sham+ND组（P<0.05），且OVX+HFD组中的FABP1、PLTP表达水平均高于OVX+ND组、sham+HFD组，PPARα低于OVX+ND组、sham+HFD组（P<0.05）。结论雌激素缺乏联合ND即可导致肝脏脂肪堆积，从而引起PMFLD，此时机体对胰岛素敏感；雌激素缺乏联合HFD可加剧PMFLD，并引发胰岛素抵抗。与PC代谢紊乱相关的FABP1-PPARα-PLTP信号通路异常可能是导致PMFLD发生的重要机制。

Abstract

Objective To establish a mouse model of perimenopausal fatty liver disease (PMFLD) using bilateral ovariectomy (OVX), and explore its pathogenesis by observing the effects of high-fat diet (HFD).Methods Twenty-four 12-week-old female C57BL/6J mice were randomly divided into 4 groups (n=6) on 2 weeks after OVX: sham operation (sham) + normal chow diet (ND) group, OVX + ND group, sham + HFD group and OVX + HFD group. All groups were evaluated at the 4th week of intervention.Results The body weight gain, visceral white adipose tissue (vWAT) weight, inguinal white adipose tissue (iWAT) weight and their proportion of body weight in the OVX + ND group were significantly higher than those in the sham + ND group; additionally, the liver Oil Red O staining ratio increased, AST and ALT level elevated, and the number of lipid droplets (LDs) in vWAT within the visual field decreased, indicating successful establishment of the PMFLD model. Liver-targeted lipidomics detection showed that only 3 phosphatidylcholines (PCs) were different across all groups, and the PC levels in the OVX + ND group and OVX + HFD group were higher than those in the sham + ND group (P<0.05). Compared with the sham + ND group, the areas under the curve (AUC) of OGTT in the OVX + ND group, sham + HFD group, and OVX + HFD group were significantly increased (P<0.05). The AUC of OGTT in the OVX + HFD group was higher than that in the OVX + ND group and sham + HFD group (P<0.05). The AUC of IRT in the sham + HFD group was higher than that in the sham + ND group, OVX + ND group, and OVX + HFD group (P<0.05). The AUC of IRT in the OVX + HFD group was higher than that in the OVX + ND group, but lower than that in the sham + HFD group (P<0.05). The expression level of FABP1 and PLTP in the OVX + ND group, sham + HFD group, and OVX + HFD group were higher than those in the sham + ND group, and the expression level of PPARα was lower than that in the sham + ND group (P<0.05). The expression level of FABP1 and PLTP in the OVX + HFD group were higher than those in the OVX + ND group and sham + HFD group, and PPARα was lower than those in the OVX + ND group and sham + HFD group (P<0.05).Conclusion Estrogen deficiency combined with ND induces hepatic lipid accumulation, thereby causing PMFLD, and the body remains insulin-sensitive at this stage. However, estrogen deficiency combined with HFD exacerbates PMFLD and induces insulin resistance. Abnormal FABP1-PPARα-PLTP signaling pathway associated with PC metabolism disorder may be an important mechanism underlying the development of PMFLD.

导出引用

张伟石晶晶王杉王亚运王松李硕秦丽华赵林华. 高脂饮食对围绝经期脂肪性肝病小鼠肝脏脂质代谢的影响[J]. 解剖学报. 2026, 57(1): 105-115 https://doi.org/10.16098/j.issn.0529-1356.2026.01.016

ZHANG Wei, SHI Jing-jing, WANG Shan, WANG Ya-yun, WANG Song, LI Shuo, QIN Li-hua, ZHAO Lin-hua. High-fat diet inducing hepatic lipid metabolism disorder in perimenopausal fatty liver disease mice[J]. Acta Anatomica Sinica. 2026, 57(1): 105-115 https://doi.org/10.16098/j.issn.0529-1356.2026.01.016

中图分类号： R326 R587.1

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