Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada.
Front Endocrinol (Lausanne). 2022 Aug 22;13:957182. doi: 10.3389/fendo.2022.957182. eCollection 2022.
The sarco(endo)plasmic reticulum Ca ATPase (SERCA) pump is responsible for the transport of Ca from the cytosol into the sarcoplasmic reticulum at the expense of ATP, making it a regulator of both muscle relaxation and muscle-based energy expenditure. Neurogranin (Ng) is a small protein that negatively regulates calcineurin signaling. Calcineurin is Ca/calmodulin dependent phosphatase that promotes the oxidative fibre type in skeletal muscle and regulates muscle-based energy expenditure. A recent study has shown that calcineurin activation reduces SERCA Ca transport efficiency, ultimately raising energy expenditure. Since the biomedical view of obesity states that it arises as an imbalance between energy intake and expenditure which favors the former, we questioned whether heterozygous Ng deletion ( ) would reduce SERCA efficiency and increase energy expenditure in female mice fed a high-fat diet (HFD). Young (3-4-month-old) female wild type (WT) and mice were fed a HFD for 12 weeks with their metabolic profile being analyzed using metabolic cages and DXA scanning, while soleus SERCA efficiency was measured using SERCA specific Ca uptake and ATPase activity assays. mice showed significantly less cage ambulation compared to WT mice but this did not lead to any added weight gain nor changes in daily energy expenditure, glucose or insulin tolerance despite a similar level of food intake. Furthermore, we observed significant reductions in SERCA's apparent coupling ratio which were associated with significant reductions in SERCA1 and phospholamban content. Thus, our results show that Ng regulates SERCA pump efficiency, and future studies should further investigate the potential cellular mechanisms.
肌浆网 Ca2+-ATP 酶（SERCA）泵负责将 Ca2+从细胞质转运到肌浆网，消耗 ATP，因此它是肌肉松弛和肌肉能量消耗的调节剂。神经颗粒蛋白（Ng）是一种负调节钙调神经磷酸酶信号的小蛋白。钙调神经磷酸酶是一种 Ca2+/钙调蛋白依赖性磷酸酶，可促进骨骼肌中氧化纤维型的形成，并调节肌肉能量消耗。最近的一项研究表明，钙调神经磷酸酶的激活降低了 SERCA 的 Ca2+转运效率，最终增加了能量消耗。由于肥胖的生物医学观点认为，它是由于能量摄入和支出之间的不平衡而产生的，这种不平衡有利于前者，因此我们质疑杂合性 Ng 缺失（）是否会降低雌性高脂肪饮食（HFD）喂养小鼠的 SERCA 效率并增加能量消耗。年轻（3-4 月龄）雌性野生型（WT）和 Ng 小鼠被喂食 HFD 12 周，使用代谢笼和 DXA 扫描分析其代谢特征，而比目鱼肌 SERCA 效率则使用 SERCA 特异性 Ca2+摄取和 ATPase 活性测定来测量。Ng 小鼠的笼内活动明显少于 WT 小鼠，但这并没有导致体重增加或每日能量消耗、葡萄糖或胰岛素耐量的变化，尽管它们的食物摄入量相似。此外，我们观察到 SERCA 的表观偶联比显著降低，这与 SERCA1 和肌浆网磷蛋白含量的显著降低有关。因此，我们的结果表明 Ng 调节 SERCA 泵的效率，未来的研究应进一步探讨潜在的细胞机制。
