Department of Pathology, The General Hospital of Western Theater Command, Chengdu, 610083, China; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
Free Radic Biol Med. 2019 Sep;141:372-382. doi: 10.1016/j.freeradbiomed.2019.07.006. Epub 2019 Jul 7.
While cardiac hypertrophy and heart failure are accompanied by significant alterations in energy metabolism, more than 50-70% of energy is obtained from fatty acid β-oxidation (FAO) in adult hearts under physiological conditions. Plin5 is involved in the metabolism of lipid droplets (LDs) and is highly abundant in oxidative tissues including heart, liver and skeletal muscle. Plin5 protects the storage of triglyceride (TG) in LDs by inhibiting lipolysis, thereby suppressing excess FAO and preventing excessive oxidative stress in the heart. In this study, we investigated the roles of Plin5 in cardiac hypertrophy and heart failure in mice treated with transverse aortic constriction (TAC). The results indicated that Plin5 deficiency aggravated myocardial hypertrophy in the TAC-treated mice and exacerbated the TAC-induced heart failure. We also found that Plin5 deficiency reduced the cardiac lipid accumulation and upregulated the levels of PPARα and PGC-1α, which stimulate mitochondrial proliferation. Moreover, Plin5 deficiency aggravated the TAC-induced oxidative stress. We consistently found that Plin5 knockdown disrupted TG storage and elevated FAO and lipolysis in H9C2 rat cardiomyocytes. In addition, Plin5 knockdown also provoked mitochondrial proliferation and lipotoxic injury in H9C2 cells. In conclusion, Plin5 deficiency increases myocardial lipolysis, elevates FAO and oxidative burden, and thereby exacerbates cardiac hypertrophy and heart failure in TAC-treated mice.
虽然心脏肥大和心力衰竭伴随着能量代谢的显著改变，但在生理条件下，成年心脏超过 50-70%的能量来自脂肪酸β氧化（FAO）。Plin5 参与脂滴（LDs）的代谢，在包括心脏、肝脏和骨骼肌在内的氧化组织中高度丰富。Plin5 通过抑制脂肪分解来保护 TG 在 LDs 中的储存，从而抑制 FAO 的过度增加，并防止心脏中过度的氧化应激。在这项研究中，我们研究了 Plin5 在 TAC 处理的小鼠心脏肥大和心力衰竭中的作用。结果表明，Plin5 缺乏加重了 TAC 处理小鼠的心肌肥大，并加剧了 TAC 诱导的心力衰竭。我们还发现 Plin5 缺乏减少了心脏脂质积累，并上调了刺激线粒体增殖的 PPARα 和 PGC-1α 的水平。此外，Plin5 缺乏加重了 TAC 诱导的氧化应激。我们一致发现 Plin5 敲低破坏了 TG 储存，并增加了 H9C2 大鼠心肌细胞中的 FAO 和脂肪分解。此外，Plin5 敲低还在 H9C2 细胞中引发了线粒体增殖和脂毒性损伤。总之，Plin5 缺乏增加心肌脂肪分解，增加 FAO 和氧化负担，从而加剧 TAC 处理小鼠的心脏肥大和心力衰竭。
