Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice.

Autor: Jian L; 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., Gao X; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Wang C; Department of Pathology, The General Hospital of Western Theater Command, Chengdu, 610083, China., Sun X; Department of CardiologyXijing Hospital, Fourth Military Medical University, Xi'an, 710032, China., Xu Y; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Han R; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Wang Y; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Xu S; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Ding L; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Zhou J; Department of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Gu Y; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Zhao Y; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Yang Y; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Yuan Y; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Ye J; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. yejing@fmmu.edu.cn., Zhang L; Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China. zhanglijun_fmmu@163.com.
Jazyk: angličtina
Zdroj: Biology direct [Biol Direct] 2023 Sep 04; Vol. 18 (1), pp. 54. Date of Electronic Publication: 2023 Sep 04.
DOI: 10.1186/s13062-023-00411-8
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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