Jain Unnati, Srivastava Priyanka, Sharma Ashwani, Sinha Subrata, Johari Surabhi
Department of Biosciences, Institute of Management Studies Ghaziabad (University Courses Campus), NH09, Adhyatmik Nagar, Ghaziabad, Uttar Pradesh, India.
Insight BioSolutions, Rue Joseph Colin, 35000 Rennes, France.
Curr Diabetes Rev. 2025;21(5):e260424229342. doi: 10.2174/0115733998265915231116043813.
The Central nervous system (CNS) is the prime regulator of signaling pathways whose function includes regulation of food intake (consumption), energy expenditure, and other metabolic responses like glycolysis, gluconeogenesis, fatty acid oxidation, and thermogenesis that have been implicated in chronic inflammatory disorders. Type 2 diabetes mellitus (T2DM) and obesity are two metabolic disorders that are linked together and have become an epidemic worldwide, thus raising significant public health concerns. Fibroblast growth factor 21 (FGF21) is an endocrine hormone with pleiotropic metabolic effects that increase insulin sensitivity and energy expenditure by elevating thermogenesis in brown or beige adipocytes, thus reducing body weight and sugar intake. In contrast, during starvation conditions, FGF21 induces its expression in the liver to initiate glucose homeostasis. Insulin resistance is one of the main anomalies caused by impaired FGF21 signaling, which also causes abnormal regulation of other signaling pathways. Tumor necrosis factor alpha (TNF-α), the cytokine released by adipocytes and inflammatory cells in response to chronic inflammation, is regarded major factor that reduces the expression of FGF21 and modulates underlying insulin resistance that causes imbalanced glucose homeostasis. This review aims to shed light on the mechanisms underlying the development of insulin resistance in obese individuals as well as the fundamental flaw in type 2 diabetes, which is malfunctioning obese adipose tissue.
中枢神经系统（CNS）是信号通路的主要调节者，其功能包括调节食物摄入（消耗）、能量消耗以及其他代谢反应，如糖酵解、糖异生、脂肪酸氧化和产热，这些代谢反应与慢性炎症性疾病有关。2型糖尿病（T2DM）和肥胖是两种相互关联的代谢紊乱疾病，已在全球范围内流行，因此引起了重大的公共卫生关注。成纤维细胞生长因子21（FGF21）是一种具有多效性代谢作用的内分泌激素，它通过提高棕色或米色脂肪细胞的产热来增加胰岛素敏感性和能量消耗，从而减轻体重和减少糖分摄入。相反，在饥饿状态下，FGF21会诱导其在肝脏中的表达以启动葡萄糖稳态。胰岛素抵抗是FGF21信号受损导致的主要异常之一，它还会导致其他信号通路的异常调节。肿瘤坏死因子α（TNF-α）是脂肪细胞和炎症细胞在慢性炎症反应中释放的细胞因子，被认为是降低FGF21表达并调节潜在胰岛素抵抗从而导致葡萄糖稳态失衡的主要因素。本综述旨在阐明肥胖个体胰岛素抵抗发展的潜在机制以及2型糖尿病的根本缺陷，即肥胖脂肪组织功能失调。
