Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Shaanxi Provincial Corps, Chinese People's Armed Police Force, Xi'an, 710054, China.
Biol Direct. 2023 Sep 4;18(1):54. doi: 10.1186/s13062-023-00411-8.
Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated.
Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes.
Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice.
Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart.
脂滴包被蛋白 5（Plin5）在维持细胞内脂滴（LDs）的稳定性和调节氧化组织中的脂肪酸代谢方面起着重要作用。它在心脏中高度表达，但它的作用尚未完全阐明。
生成 Plin5 缺陷型小鼠和 Plin5/瘦素双敲除小鼠，观察其组织学结构和心肌功能。在心脏组织、新生鼠心肌细胞和过表达 Plin5 的 H9C2 细胞中测量与脂肪酸和葡萄糖代谢相关的关键蛋白。采用 2-NBDG 检测葡萄糖摄取。通过 MitoTracker 和 BODIPY 493/503 染色观察新生鼠心肌细胞中的线粒体和脂质含量。
Plin5 缺乏会损害小鼠心肌细胞中的葡萄糖利用并导致胰岛素抵抗，尤其是在存在脂肪酸（FAs）的情况下。此外，Plin5 缺乏增加了心肌细胞中的 NADH 含量并上调了乳酸脱氢酶（LDHA）的表达，导致乳酸生成增加。此外，当脂肪酸氧化被 etomoxir 阻断或 LDHA 在 Plin5 缺陷型心肌细胞中被 GSK2837808A 抑制时，葡萄糖利用得到改善。瘦素缺乏型小鼠表现出心肌肥厚、胰岛素抵抗和底物利用改变，Plin5 缺乏加剧了瘦素缺乏型小鼠的心肌肥厚。
我们的研究结果表明，Plin5 在协调心肌细胞中脂肪酸和葡萄糖氧化方面起着关键作用，为治疗心脏代谢紊乱提供了一个潜在的靶点。
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