Female mice exposed to varying ratios of stearic to palmitic acid in a high-fat diet during gestation and lactation shows differential impairments of beta-cell function

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-03-06 DOI:10.1016/j.lfs.2025.123532

Chenchen Geng , Xiaohan Li , Lingfeng Dan , Liyan Xie , Min Zhou , Kaile Guan , Qi Chen , Yan Xu , Rong Ding , Jiaqi Li , Yue Zhang , Mohammad Sharifzadeh , Rui Liu , Wenting Li , Huimin Lu

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引用次数: 0

Abstract

Aims

While emerging evidence implicates an abnormal stearic-to-palmitic acid ratio in saturated fats in beta-cell dysfunction, their gestational/lactational impacts remain underexplored. This study evaluates the differential transient and long-lasting effects of high-fat diets with contrasting stearic-to-palmitic acid ratios on maternal beta-cell function.

Materials and methods

Female mice were fed high-fat diets with high/low stearic-to-palmitic acid ratios during gestation/lactation, followed by a recovery period and subsequent exposure to an obesogenic diet. Beta-cell function was assessed using ex-vivo glucose-stimulated insulin secretion (GSIS) and immunohistochemistry. Islets mRNA profiling was performed using RNA-sequencing.

Key findings

Both high- and low-ratio groups showed impaired GSIS post-lactation. High-ratio-fed dams exhibited pronounced compensatory responses, including increased islet size, number, and elevated Stx1a, Stx4, Pdx1, Mafa expression. Following metabolic re-challenge, high-ratio group demonstrated more severely impaired ex vivo insulin release. No significant differences in islet apoptosis and senescence were observed between the two groups. Transcriptomic profiling, however, revealed distinct mechanistic pathways: the high-ratio diet was likely to disrupt beta-cell organelles ultrastructure, while the low-ratio diet predominantly dysregulated chemokine-mediated immune signaling networks.

Significance

Gestational/lactational exposure to high-fat diets with both high and low ratios of stearic-to-palmitic acid exerts pronounced transient impacts on beta-cell function, with the high-ratio diet inducing more severe and persistent detrimental effects. These findings highlight the critical influence and importance of dietary saturated fatty acid composition in maternal metabolic programming and beta-cell vulnerability.

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雌性小鼠在妊娠期和哺乳期暴露于不同比例的硬脂酸和棕榈酸的高脂肪饮食中，表现出不同程度的细胞功能损伤

虽然新出现的证据表明饱和脂肪中硬脂酸与棕榈酸的比例异常与β细胞功能障碍有关，但它们在妊娠期/哺乳期的影响仍未得到充分研究。本研究评估了高脂肪饮食对母体β细胞功能的短期和长期影响，并对比了硬脂酸与棕榈酸的比例。材料和方法雌性小鼠在妊娠/哺乳期饲喂高脂/低硬脂/棕榈酸比的高脂饲料，随后进行恢复期和随后的致肥性饮食。利用体外葡萄糖刺激胰岛素分泌（GSIS）和免疫组织化学评估β细胞功能。使用rna测序进行胰岛mRNA谱分析。主要发现：高比例组和低比例组均显示泌乳后GSIS受损。高比例喂养的水坝表现出明显的代偿反应，包括增加胰岛的大小和数量，提高Stx1a、Stx4、Pdx1和Mafa的表达。代谢再激发后，高比值组体外胰岛素释放受损更严重。两组小鼠胰岛细胞凋亡及衰老无明显差异。然而，转录组分析揭示了不同的机制途径：高比例饮食可能破坏β细胞器超微结构，而低比例饮食主要失调趋化因子介导的免疫信号网络。妊娠/哺乳期暴露于高脂饮食中，无论是高脂/棕榈酸比例还是低脂/棕榈酸比例，都会对β细胞功能产生明显的短暂影响，高脂/棕榈酸比例的饮食会产生更严重和持久的有害影响。这些发现强调了饮食饱和脂肪酸组成对母体代谢程序和β细胞脆弱性的关键影响和重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.