Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India.
Front Endocrinol (Lausanne). 2024 Oct 30;15:1383520. doi: 10.3389/fendo.2024.1383520. eCollection 2024.
Diabesity, characterized by obesity-driven Type 2 diabetes mellitus (T2DM), arises from intricate genetic and environmental interplays that induce various metabolic disorders. The systemic lipid and glucose homeostasis is controlled by an intricate cross-talk of internal glucose/insulin and fatty acid molecules to maintain a steady state of internal environment.
In this study, were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients to delve into the mechanistic foundations of diabesity. Various assays were conducted to measure intracellular triglyceride levels, lifespan, pharyngeal pumping rate, oxidative stress indicators, locomotor behavior, and dopamine signaling. Proteomic analysis was also performed to identify differentially regulated proteins and dysregulated KEGG pathways, and microscopy and immunofluorescence staining were employed to assess collagen production and anatomical integrity.
Worms raised on diets high in glucose and cholesterol exhibited notably increased intracellular triglyceride levels, a decrease in both mean and maximum lifespan, and reduced pharyngeal pumping. The diabesity condition induced oxidative stress, evident from heightened ROS levels and distinct FT-IR spectroscopy patterns revealing lipid and protein alterations. Furthermore, impaired dopamine signaling and diminished locomotors behavior in diabesity-afflicted worms correlated with reduced motility. Through proteomic analysis, differentially regulated proteins encompassing dysregulated KEGG pathways included insulin signaling, Alzheimer's disease, and nicotinic acetylcholine receptor signaling pathways were observed. Moreover, diabesity led to decreased collagen production, resulting in anatomical disruptions validated through microscopy and immunofluorescence staining.
This underscores the impact of diabesity on cellular components and structural integrity in , providing insights into diabesity-associated mechanisms.
以肥胖为特征的糖尿病（2 型糖尿病）是由复杂的遗传和环境相互作用引起的，导致各种代谢紊乱。系统的脂质和葡萄糖稳态是由内部葡萄糖/胰岛素和脂肪酸分子的复杂串扰控制的，以维持内部环境的稳定状态。
在这项研究中，我们维持高血糖条件，以深入研究糖尿病的发病机制。进行了各种测定，以测量细胞内甘油三酯水平、寿命、咽泵速率、氧化应激指标、运动行为和多巴胺信号。还进行了蛋白质组学分析，以鉴定差异调节的蛋白质和失调的 KEGG 途径，并进行显微镜和免疫荧光染色，以评估胶原蛋白产生和解剖完整性。
在高葡萄糖和胆固醇饮食中饲养的蠕虫表现出明显增加的细胞内甘油三酯水平、平均和最大寿命降低以及咽泵减少。糖尿病状态诱导氧化应激，从 ROS 水平升高和独特的 FT-IR 光谱模式显示脂质和蛋白质改变中可以看出。此外，糖尿病影响的蠕虫中的多巴胺信号受损和运动行为减弱与运动能力降低相关。通过蛋白质组学分析，观察到包含失调的 KEGG 途径的胰岛素信号、阿尔茨海默病和烟碱型乙酰胆碱受体信号通路的差异调节蛋白。此外，糖尿病导致胶原蛋白产生减少，通过显微镜和免疫荧光染色验证了结构破坏。
这强调了糖尿病对秀丽隐杆线虫细胞成分和结构完整性的影响，为糖尿病相关机制提供了见解。
