There is a gap in the knowledge regarding regulation of local renin–angiotensin system (RAS) in skeletal muscle during development of obesity and insulin resistance in vivo. This study evaluates the obesity- and age-related changes in the expression of local RAS components. Since RAS affects skeletal muscle remodelling, we also evaluated the muscle fibre type composition, defined by myosin heavy chain (MyHC) mRNAs and protein content. Gene expressions were determined by qPCR and/or Western blot analysis in musculus quadriceps of 3- and 8-month-old male obese Zucker rats and their lean controls. The enzymatic activity of aminopeptidase A (APA) was determined flourometrically. Activation of renin receptor (ReR)/promyelocytic leukaemia zinc finger (PLZF) negative feedback mechanism was observed in obesity. The expression of angiotensinogen and AT1 was downregulated by obesity, while neutral endopeptidase and AT2 expressions were upregulated in obese rats with aging. Skeletal muscle APA activity was decreased by obesity, which negatively correlated with the increased plasma APA activity and plasma cholesterol. The expression of angiotensin-converting enzyme (ACE) positively correlated with MyHC mRNAs characteristic for fast-twitch muscle fibres. The obesity- and age-related alterations in the expression of both classical and alternative RAS components suggest an onset of a new equilibrium between ACE/AngII/AT1 and ACE2/Ang1–7/Mas at lower level accompanied by increased renin/ReR/PLZF activation. Increased APA release from the skeletal muscle in obesity might contribute to increased plasma APA activity. There is a link between reduced ACE expression and altered muscle MyHC proportion in obesity and aging.

中文翻译：

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肥胖和衰老会影响糖尿病前期祖克大鼠的骨骼肌肾素-血管紧张素系统和肌球蛋白重链比例。

在体内肥胖和胰岛素抵抗的发展过程中，骨骼肌局部肾素-血管紧张素系统（RAS）调控的知识尚不完善。这项研究评估与肥胖和年龄有关的局部RAS成分表达的变化。由于RAS影响骨骼肌重塑，我们还评估了肌纤维类型组成，由肌球蛋白重链（MyHC）mRNA和蛋白质含量定义。通过qPCR和/或蛋白质印迹分析，在3月龄和8月龄雄性肥胖祖克大鼠及其瘦弱对照的四头肌小肌中确定基因表达。荧光测定氨基肽酶A（APA）的酶活性。在肥胖症中观察到肾素受体（ReR）/早幼粒细胞白血病锌指（PLZF）激活的负反馈机制。肥胖使血管紧张素原和AT1的表达下调，而衰老的肥胖大鼠中性内肽酶和AT2的表达上调。肥胖会降低骨骼肌APA活性，这与血浆APA活性和血浆胆固醇的升高呈负相关。血管紧张素转换酶（ACE）的表达与快肌纤维的MyHC mRNA呈正相关。肥胖和与年龄有关的经典和替代RAS成分表达变化表明，较低水平的ACE / AngII / AT1和ACE2 / Ang1-7 / Mas之间出现新的平衡，同时伴有肾素/ ReR / PLZF升高激活。肥胖中骨骼肌APA释放增加可能有助于血浆APA活性增加。