This study investigated whether oxidative and glycolytic rat skeletal muscles respond differently to a high-fat (HF) sucrose-enriched diet with respect to diacylglycerol (DAG) and ceramides accumulation, protein kinase C (PKC) activation, glucose metabolism, and the expression of inflammatory genes. HF diet (8 weeks) suppressed insulin-stimulated glycogen synthesis and glucose oxidation in soleus (Sol), extensor digitorum longus (EDL) and epitrochlearis (Epit) muscles. However, DAG and ceramides levels increased in Sol and EDL, but not in Epit muscles of HF-fed rats. Additionally, membrane-bound PKC-delta and PKC-theta increased in Sol and EDL, whereas in Epit muscles both PKC isoforms were reduced by HF diet. In Epit muscles, HF diet also increased the expression of tumor necrosis factor-α (TNF-α) receptors (CD40 and FAS), toll-like receptor 4 (TLR4), and nuclear factor kappa light polypeptide gene enhancer in B cells (NF-kB), whereas in Sol and EDL muscles the expression of these inflammatory genes remained unchanged upon HF feeding. In conclusion, HF diet caused DAG and ceramides accumulation, PKC activation, and the induction of inflammatory pathways in a fiber type-specific manner. These findings help explain why oxidative and glycolytic muscles similarly develop insulin resistance, despite major differences in their metabolic characteristics and responsiveness to dietary lipid abundance.

本研究调查了氧化和糖酵解大鼠骨骼肌是否对高脂肪 (HF) 富含蔗糖的饮食在二酰基甘油 (DAG) 和神经酰胺积累、蛋白激酶 C (PKC) 激活、葡萄糖代谢和炎症基因。HF 饮食（8 周）抑制了比目鱼肌 (Sol)、趾长伸肌 (EDL) 和滑车上肌 (Epit) 中胰岛素刺激的糖原合成和葡萄糖氧化。然而，DAG 和神经酰胺水平在 Sol 和 EDL 中增加，但在 HF 喂养大鼠的 Epit 肌肉中没有增加。此外，膜结合 PKC-delta 和 PKC-theta 在 Sol 和 EDL 中增加，而在 Epit 肌肉中，两种 PKC 异构体​​都因 HF 饮食而减少。在 Epit 肌肉中，HF 饮食还增加了肿瘤坏死因子-α（TNF-α）受体（CD40 和 FAS）的表达，Toll 样受体 4 (TLR4) 和 B 细胞中的核因子κ轻多肽基因增强子 (NF-kB)，而在 Sol 和 EDL 肌肉中，这些炎症基因的表达在 HF 喂养时保持不变。总之，HF 饮食以纤维类型特异性方式引起 DAG 和神经酰胺积累、PKC 激活和炎症通路的诱导。这些发现有助于解释为什么氧化肌和糖酵解肌同样会产生胰岛素抵抗，尽管它们的代谢特征和对膳食脂质丰度的反应存在重大差异。以及以纤维类型特异性方式诱导炎症通路。这些发现有助于解释为什么氧化肌和糖酵解肌同样会产生胰岛素抵抗，尽管它们的代谢特征和对膳食脂质丰度的反应存在重大差异。以及以纤维类型特异性方式诱导炎症通路。这些发现有助于解释为什么氧化肌和糖酵解肌同样会产生胰岛素抵抗，尽管它们的代谢特征和对膳食脂质丰度的反应存在重大差异。