Rehman Asim, Bukhari Shazia Anwer, Chauhdary Zunera, Akhter Naheed, Noreen Razia
Department of Biochemistry, Government College University, Faisalabad, Pakistan.
Department of Pharmacology, Government College University, Faisalabad, Pakistan.
Biochem Biophys Res Commun. 2025 May 1;761:151748. doi: 10.1016/j.bbrc.2025.151748. Epub 2025 Apr 2.
The concurrent presence of complex metabolic disorders such as obesity and diabetes within an individual is known as diabesity. Various organs are involved in metabolic chronic diseases like obesity, hypertension, and diabetes. In the last few years, the rise in diabetes cases has coincided with the rapid elevation in obesity rates, resulting in a global health crisis. Major risk factors playing a critical role in the spread of obesity include high-fat food consumption, high-calorie foods, and insufficient physical activity. Diabetes is strongly linked with obesity in terms of metabolic abnormalities and physiological processes, including inflammation. Diabetes type 2 (T2D) is caused primarily by insulin resistance and insufficient insulin release from beta cells of the pancreas. An obese or overweight individual has a strong association with insulin resistance, which in turn leads to the development of T2D. Metabolic stress due to nutrient overload releases different types of inflammatory mediators (such as TNF-α, IL-6, and SFRP4) from adipose tissues in obesity. Secreted frizzled-related protein 4 (SFRP4) is also an inflammatory mediator that impairs insulin secretion. SFRP4 acts as an early biomarker for diabesity expressed with interleukin-1 beta (IL-1β) in the adipose tissues that hinders the exocytosis of insulin-secreting granules from the pancreatic β-cells and is a potential target for preserving β-cell dysfunction and the diabesity treatment. In the current study, plant-based phytocompounds were identified and investigated in silico and in vivo for their ability to suppress the expression of SFRP4. In a diet-induced mouse model, short-listed compounds such as resveratrol and quercetin at higher and lower doses were found effective and significant in reducing the anti-inflammatory mediators and SFRP4 levels. Overall, the current study describes the expression of SFRP4, IL-6, and TNF-α, and its inhibition by various inhibitors. Moreover, the study's findings suggest that resveratrol and quercetin hold promise as potential treatments for diabesity.
个体同时存在肥胖和糖尿病等复杂代谢紊乱的情况被称为糖尿病型肥胖症。肥胖、高血压和糖尿病等代谢性慢性疾病涉及多个器官。在过去几年中，糖尿病病例的增加与肥胖率的迅速上升同时出现，导致了一场全球健康危机。在肥胖传播中起关键作用的主要风险因素包括高脂肪食物消费、高热量食物以及体育活动不足。糖尿病在代谢异常和生理过程（包括炎症）方面与肥胖密切相关。2型糖尿病（T2D）主要由胰岛素抵抗和胰腺β细胞胰岛素分泌不足引起。肥胖或超重个体与胰岛素抵抗密切相关，进而导致T2D的发生。肥胖中营养过剩引起的代谢应激会从脂肪组织中释放不同类型的炎症介质（如TNF-α、IL-6和SFRP4）。分泌型卷曲相关蛋白4（SFRP4）也是一种炎症介质，会损害胰岛素分泌。SFRP4作为糖尿病型肥胖症的早期生物标志物，与脂肪组织中的白细胞介素-1β（IL-1β）共同表达，阻碍胰腺β细胞胰岛素分泌颗粒的胞吐作用，是预防β细胞功能障碍和糖尿病型肥胖症治疗的潜在靶点。在当前的研究中，基于植物的植物化合物在计算机模拟和体内实验中被鉴定和研究，以评估它们抑制SFRP4表达的能力。在饮食诱导的小鼠模型中，发现白藜芦醇和槲皮素等入围化合物在高剂量和低剂量时均能有效且显著地降低抗炎介质和SFRP4水平。总体而言，当前的研究描述了SFRP4、IL-6和TNF-α的表达以及它们被各种抑制剂抑制的情况。此外，该研究的结果表明，白藜芦醇和槲皮素有望成为糖尿病型肥胖症的潜在治疗方法。
