Evidence for increased and insulin-resistant lipolysis in skeletal muscle of high-fat-fed rats.
Evidence for increased and insulin-resistant lipolysis in skeletal muscle of high-fat-fed rats.
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DOI：
10.1016/j.metabol.2003.11.029
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发表时间：
2004-06
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采用清醒、空腹瘦和高脂诱导的肥胖大鼠检测骨骼肌中甘油的代谢和同位素谱，并进行高胰岛素-正葡萄糖钳夹以评估胰岛素的作用。钳夹期间，同时输注Intraperoid（无肝素; Fresnius Kabi克莱顿，克莱顿，NC）、游离脂肪酸、甘油和葡萄糖，以维持两组中各自的基础血浆水平。在稳态时，静脉输注[U-14 C]甘油120分钟，然后进行肌肉活检。在肥胖大鼠中观察到肥胖的经典表型特征，即胰岛素刺激的葡萄糖摄取减少，胰岛素不能抑制全身脂解，以及血浆脂肪酸浓度升高。新的观察表明，在基础状态下，同位素比活度（S.A.）在腓肠肌（0.03 v0.12）、比目鱼肌（0.05 v0.12）和胫骨前肌（0.03 v0.12）中的甘油浓度（dpm/nmol）在肥胖大鼠中显著低于瘦大鼠（均P <0.003），尽管浓度相似，表明基础肌细胞内脂解活跃。此外，脂肪分解似乎对胰岛素有抵抗性，因为在钳夹过程中，肥胖组的肌肉甘油抑制率分别为8%、12%和8%，而瘦对照组的腓肠肌（P = 0.001）、比目鱼肌（P = 0.007）和胫骨前肌（P = 0.004）分别为67%、71%和63%。活跃的细胞内脂肪分解可能干扰可能导致胰岛素抵抗的代谢功能。
The metabolic and isotopic profiles of glycerol in skeletal muscle were examined using awake, fasted lean and high-fat-induced obese rats, and hyperinsulinemic-euglycemic clamp was performed to assess the effect of insulin. During the clamp, Intralipid (no heparin; Fresnius Kabi Clayton, Clayton, NC), free fatty acids, glycerol, and glucose were coinfused to maintain their respective basal plasma levels in both groups. At steady-state, [U-14C]glycerol was infused intravenously for 120 minutes followed by muscle biopsy. The classical phenotypic characteristics of obesity, namely, reduced insulin-stimulated glucose uptake, a failure to suppress systemic lipolysis by insulin, and elevated plasma fatty acid concentration, were observed in the obese rats. Novel observations showed that in the basal state, the isotopic specific activity (S.A.) of glycerol (dpm/nmol) in gastrocnemius (0.03 v 0.12), soleus (0.05 v 0.12), and tibialis anterior (0.03 v 0.12) was significantly lower (all P < .003) in obese than in lean rats despite similar concentrations, indicating an active basal intramyocellular lipolysis. In addition, the lipolysis appeared resistant to insulin because the suppression of muscle glycerol during the clamp was 8%, 12%, and 8% in obese compared to 67%, 71%, and 63% in the lean control for gastrocnemius (P = .001), soleus (P = .007), and tibialis anterior (P = .004), respectively. The active intracellular lipolysis likely disturbs metabolic functions that may contribute to insulin resistance.