Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway; Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Norway.
Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Norway.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Apr;1866(4):158873. doi: 10.1016/j.bbalip.2020.158873. Epub 2020 Dec 26.
Plin5 is abundantly expressed in the heart where it binds to lipid droplets (LDs) and facilitates physical interaction between LDs and mitochondria. We isolated cardiomyocytes from adult Plin5 and Plin5 mice to study the role of Plin5 for fatty acid uptake, LD accumulation, fatty acid oxidation, and tolerance to hypoxia. Cardiomyocytes isolated from Plin5 mice cultured with oleic acid stored less LDs than Plin5, but comparable levels to Plin5 cardiomyocytes when adipose triglyceride lipase activity was inhibited. The ability to oxidize fatty acids into CO was similar between Plin5 and Plin5 cardiomyocytes, but Plin5 cardiomyocytes had a transient increase in intracellular fatty acid oxidation intermediates. After pre-incubation with oleic acids, Plin5 cardiomyocytes retained a higher content of glycogen and showed improved tolerance to hypoxia compared to Plin5. In isolated, perfused hearts, deletion of Plin5 had no important effect on ventricular pressures or infarct size after ischemia. Old Plin5 mice had reduced levels of cardiac triacylglycerides, increased heart weight, and apart from modest elevated expression of mRNAs for beta myosin heavy chain Myh7 and the fatty acid transporter Cd36, other genes involved in fatty acid oxidation, glycogen metabolism and glucose utilization were essentially unchanged by removal of Plin5. Plin5 seems to facilitate cardiac LD storage primarily by repressing adipose triglyceride lipase activity without altering cardiac fatty acid oxidation capacity. Expression of Plin5 and cardiac LD content of isolated cardiomyocytes has little importance for tolerance to acute hypoxia and ischemia, which contrasts the protective role for Plin5 in mouse models during myocardial ischemia.
Plin5 在心脏中大量表达，它与脂滴 (LDs) 结合，并促进 LDs 与线粒体之间的物理相互作用。我们从成年 Plin5 和 Plin5 小鼠中分离出心肌细胞，以研究 Plin5 对脂肪酸摄取、LD 积累、脂肪酸氧化以及对缺氧的耐受能力的作用。在培养的油酸中，与 Plin5 相比，从 Plin5 小鼠中分离出的心肌细胞储存的 LDs 较少，但当脂肪甘油三酯酶活性受到抑制时，其储存的 LDs 水平与 Plin5 心肌细胞相当。Plin5 和 Plin5 心肌细胞氧化脂肪酸生成 CO 的能力相似，但 Plin5 心肌细胞细胞内脂肪酸氧化中间产物短暂增加。在预先用油酸孵育后，与 Plin5 相比，Plin5 心肌细胞保留了更高的糖原含量，并表现出对缺氧的耐受性提高。在分离的灌注心脏中，Plin5 的缺失对缺血后心室压力或梗死面积没有重要影响。老年 Plin5 小鼠的心脏三酰甘油水平降低，心脏重量增加，除了β肌球蛋白重链 Myh7 和脂肪酸转运蛋白 Cd36 的 mRNA 表达适度升高外，其他参与脂肪酸氧化、糖原代谢和葡萄糖利用的基因在 Plin5 缺失时基本不变。Plin5 似乎主要通过抑制脂肪甘油三酯酶的活性来促进心脏 LDs 的储存，而不改变心脏的脂肪酸氧化能力。分离的心肌细胞中 Plin5 的表达和 LDs 含量对急性缺氧和缺血的耐受性几乎没有重要意义，这与 Plin5 在心肌缺血小鼠模型中的保护作用形成对比。
