Long Caiyi, Li Zihan, Jiang Liangliang, Yang Xinyu, Deng Siyu, Jiang Yayi, Zhang Boxun, Yue Rensong
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Lipids Health Dis. 2025 Sep 23;24(1):284. doi: 10.1186/s12944-025-02747-8.
Patients with type 2 diabetes mellitus (T2DM) often exhibit dysregulated lipid metabolism, which contributes to the development and progression of complications, such as cardiomyopathy and nephropathy. Lipid droplet (LD) dynamics involve several processes, such as synthesis, lipolysis, and lipophagy. They also interact with organelles, such as the endoplasmic reticulum, mitochondria, and Golgi apparatus. These dynamic behaviors are essential for the maintenance of cellular energy homeostasis. Under physiological conditions, LDs in pancreatic β-cells are involved in lipid metabolism that regulates insulin secretion, while also isolating harmful lipids to protect β-cells from damage due to nutrient excess. In the adipose tissue, LDs respond to nutrient fluctuations by modulating lipolysis and releasing free fatty acids (FFAs) and glycerol. Glycerol can enter the liver for gluconeogenesis and changes in FFA levels affect systemic insulin sensitivity, thereby influencing glucose uptake by skeletal muscles and contributing to whole-body glucose homeostasis. Under pathological conditions, abnormal LD accumulation can lead to ectopic lipid deposition and lipotoxicity, exacerbating T2DM and its complications in target organs, such as the heart, kidneys, retina, and brain. Lifestyle interventions, such as diet and exercise, influence LD homeostasis in tissues affected by T2DM. Pharmacological agents, including certain antidiabetic and lipid-lowering drugs as well as bioactive natural products, have demonstrated tissue-specific regulatory effects on LD dynamics. Emerging therapeutic strategies targeting LDs, such as photodynamic therapy, gene editing, and gut microbiota modulation, are also being investigated. In summary, a deeper understanding of the physiological and pathological roles of LDs in different organs may offer targeted and integrated treatment options for T2DM and its associated complications.
2型糖尿病（T2DM）患者常表现出脂质代谢失调，这会促使并发症（如心肌病和肾病）的发生和发展。脂滴（LD）动态变化涉及多个过程，如合成、脂解和脂肪自噬。它们还与内质网、线粒体和高尔基体等细胞器相互作用。这些动态行为对于维持细胞能量稳态至关重要。在生理条件下，胰腺β细胞中的脂滴参与调节胰岛素分泌的脂质代谢，同时还隔离有害脂质以保护β细胞免受营养过剩造成的损害。在脂肪组织中，脂滴通过调节脂解并释放游离脂肪酸（FFA）和甘油来应对营养波动。甘油可进入肝脏进行糖异生，FFA水平的变化会影响全身胰岛素敏感性，从而影响骨骼肌对葡萄糖的摄取并有助于维持全身葡萄糖稳态。在病理条件下，异常的脂滴积累会导致异位脂质沉积和脂毒性，加剧T2DM及其在心脏、肾脏、视网膜和大脑等靶器官中的并发症。生活方式干预，如饮食和运动，会影响受T2DM影响的组织中的脂滴稳态。包括某些抗糖尿病和降脂药物以及生物活性天然产物在内的药物制剂已显示出对脂滴动态变化具有组织特异性调节作用。针对脂滴的新兴治疗策略，如光动力疗法、基因编辑和肠道微生物群调节，也正在研究中。总之，更深入地了解脂滴在不同器官中的生理和病理作用可能为T2DM及其相关并发症提供有针对性的综合治疗方案。
