Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Metabolic Vascular Disease Key Laboratory of Sichuan Province, Sichuan 646000, China.
Biosci Rep. 2023 Jul 26;43(7). doi: 10.1042/BSR20230501.
Obesity, characterized by accumulation of adipose, is usually accompanied by hyperlipidemia and abnormal glucose metabolism, which destroys the function and structure of islet β cells. However, the exact mechanism of islet deterioration caused by obesity has not yet been fully elucidated. Here, we fed C57BL/6 mice with a high-fat diet (HFD) for 2 (2M group) and 6 months (6M group) to construct obesity mouse models. Then, RNA-based sequencing was used to identify the molecular mechanisms in HFD-induced islet dysfunction. Compared with the control diet, a total of 262 and 428 differentially expressed genes (DEGs) were identified from islets of the 2M and 6M groups, respectively. GO and KEGG enrichment analysis revealed that the DEGs up-regulated in both the 2M and 6M groups are mainly enriched in response to endoplasmic reticulum stress and the pancreatic secretion pathway. DEGs down-regulated in both the 2M and 6M groups are mainly enriched in the neuronal cell body and protein digestion and absorption pathway. Notably, along with the HFD feeding, mRNA expression of islet cell markers was significantly down-regulated, such as Ins1, Pdx1, MafA (β cell), Gcg, Arx (α cell), Sst (δcell), and Ppy (PP cell). In contrast, mRNA expression of acinar cell markers was remarkably up-regulated, such as Amy1, Prss2, and Pnlip. Besides, a large number of collagen genes were down-regulated, such as Col1a1, Col6a6, and Col9a2. Overall, our study provides a full-scale DEG map regarding HFD-induced islet dysfunction, which was helpful to understand the underlying molecular mechanism of islet deterioration further.
肥胖症的特征是脂肪积累，通常伴随着血脂异常和葡萄糖代谢异常，破坏胰岛β细胞的功能和结构。然而，肥胖引起的胰岛恶化的确切机制尚未完全阐明。在这里，我们用高脂肪饮食（HFD）喂养 C57BL/6 小鼠 2（2M 组）和 6 个月（6M 组），构建肥胖小鼠模型。然后，我们使用基于 RNA 的测序来鉴定 HFD 诱导的胰岛功能障碍的分子机制。与对照饮食相比，从 2M 组和 6M 组的胰岛中分别鉴定出总共 262 和 428 个差异表达基因（DEGs）。GO 和 KEGG 富集分析表明，2M 和 6M 组中上调的 DEGs 主要富集在对内质网应激和胰腺分泌途径的反应中。在 2M 和 6M 组中下调的 DEGs 主要富集在神经元细胞体和蛋白质消化吸收途径中。值得注意的是，随着 HFD 喂养，胰岛细胞标志物的 mRNA 表达显著下调，如 Ins1、Pdx1、MafA（β 细胞）、Gcg、Arx（α 细胞）、Sst（δ 细胞）和 Ppy（PP 细胞）。相比之下，腺泡细胞标志物的 mRNA 表达显著上调，如 Amy1、Prss2 和 Pnlip。此外，大量胶原基因下调，如 Col1a1、Col6a6 和 Col9a2。总之，我们的研究提供了一个关于 HFD 诱导的胰岛功能障碍的全规模 DEG 图谱，有助于进一步了解胰岛恶化的潜在分子机制。
