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母体高脂饮食诱导子代肥胖:揭示热休克蛋白增加介导的脂肪组织功能障碍。

Maternal high-fat diet-induced obesity in offspring: Unraveling adipose tissue dysfunction mediated by increased heat shock proteins.

作者信息

Paz Henry A, Buddha Lasya, Lam Tianfu, Zhong Ying, Sikes James D, Shankar Kartik, Andres Aline, Wankhade Umesh D

机构信息

Arkansas Children's Nutrition Center, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Arkansas Children's Nutrition Center, Little Rock, AR, USA.

出版信息

Int J Biochem Cell Biol. 2025 Sep;186:106812. doi: 10.1016/j.biocel.2025.106812. Epub 2025 Jun 11.

Abstract

Maternal weight and diet before and during pregnancy have a substantial impact on offspring metabolic health, though sex-specific differences in metabolic and adipose tissue adaptations to maternal overnutrition remain insufficiently understood. Using a mouse model of maternal high-fat (HF) diet-induced obesity, this study assessed the sexually dimorphic responses on offspring adiposity, physiology, and adipose tissue function. Male offspring of HF diet-fed dams exhibited greater weight gain and adiposity, impaired glucose homeostasis, elevated serum levels of insulin, leptin, and cholesterol, along with increased adipogenic and heat shock proteins (HSPs) gene expression in white adipose tissue compared to female offspring. In established adipocyte cell lines independent of experimental animals, the expression of HSPs during differentiation was higher in white than in brown adipocytes. Also, expression of Hsp90ab1 in human umbilical cord mesenchymal stem cells tended to positively correlate with maternal body mass index in male, but not in female infants. This finding was generated independently of the animal model and were intended to strengthen the translational perspective of our work. Together, these results suggest a potential link between maternal diet, HSPs, and adipose tissue function.

摘要

孕期前后母亲的体重和饮食对后代的代谢健康有重大影响,尽管代谢和脂肪组织对母体营养过剩的适应性存在性别差异,但人们对此仍了解不足。本研究使用母体高脂(HF)饮食诱导肥胖的小鼠模型,评估了后代肥胖、生理和脂肪组织功能的性别差异反应。与雌性后代相比,喂食HF饮食的母鼠所生的雄性后代体重增加更多、脂肪堆积更多、葡萄糖稳态受损、血清胰岛素、瘦素和胆固醇水平升高,同时白色脂肪组织中的脂肪生成和热休克蛋白(HSPs)基因表达增加。在独立于实验动物的已建立的脂肪细胞系中,白色脂肪细胞在分化过程中HSPs的表达高于棕色脂肪细胞。此外,人类脐带间充质干细胞中Hsp90ab1的表达在男婴中往往与母亲体重指数呈正相关,而在女婴中则不然。这一发现独立于动物模型得出,旨在加强我们工作的转化视角。总之,这些结果表明母体饮食、HSPs和脂肪组织功能之间可能存在联系。

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