Verma Mahesh Kumar, Yateesh Aggunda Nagaraju, Smitha Rachapalli, Neelima Korrapati, Pallavi Puttrevana M, Reddy Madhusudhan, Poornima Jayaram, Oommen Anup M, Jagannath Madanahalli R, Somesh Baggavalli P
Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
Springerplus. 2014 May 18;3:251. doi: 10.1186/2193-1801-3-251. eCollection 2014.
Apart from elevated glucose, triglyceride and cholesterol, elevated levels of serum free-fatty acid (FFA) are observed in diabetic patients. Increased FFA load can cause multiple dysregulation which are collectively known as lipotoxicity. Impacts of FFA induced lipotoxicity were evaluated on various cellular responses of metabolism and stress in skeletal muscle myotubes. Under lipotoxicity, oxidative capacity of C2C12 myotubes was reduced and decreased levels ATP and NAD were observed. Lipotoxicity augmented non-oxidative disposal of metabolites in terms of lactate release, IMTG and ceramide synthesis. Concomitantly, insulin resistance was also observed. These impacts were in conjunction with increased cellular stress, inflammation, proteolysis and apoptosis. Quenching of lipotoxicity mediated oxidative stress by antioxidant reverted its deleterious impacts and restored insulin stimulated glucose uptake. In conclusion, the in vitro lipotoxicity makes a system which resembles in vivo pathology of muscle as seen in diabetic patients and represents an integrated perspective of lipotoxicity on various parameters of metabolism and stress.
除了血糖、甘油三酯和胆固醇升高外，糖尿病患者还会出现血清游离脂肪酸（FFA）水平升高的情况。游离脂肪酸负荷增加会导致多种失调，统称为脂毒性。评估了游离脂肪酸诱导的脂毒性对骨骼肌肌管代谢和应激的各种细胞反应的影响。在脂毒性作用下，C2C12肌管的氧化能力降低，ATP和NAD水平下降。脂毒性增加了代谢产物的非氧化处理，表现为乳酸释放、IMTG和神经酰胺合成增加。同时，还观察到胰岛素抵抗。这些影响与细胞应激、炎症、蛋白水解和细胞凋亡增加有关。抗氧化剂淬灭脂毒性介导的氧化应激可逆转其有害影响，并恢复胰岛素刺激的葡萄糖摄取。总之，体外脂毒性构建了一个类似于糖尿病患者体内肌肉病理的系统，并代表了脂毒性对代谢和应激各种参数的综合影响。
