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

张伟 石晶晶 王杉 王亚运 王松 李硕 秦丽华 赵林华

doi:10.16098/j.issn.0529-1356.2026.01.016

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (1) : 105-115. DOI: 10.16098/j.issn.0529-1356.2026.01.016

Histology and Embryology and Development Biology

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*

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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.

Key words

/ "> Perimenopausal fatty liver disease / Phospholipid transfer protein / High-fat diet / Phosphatidylcholine / Insulin resistance / Oral glucose tolerance test / Insulin release test / Mouse

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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

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