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Vaspin Mediates the Intraorgan Crosstalk Between Heart and Adipose Tissue in Lipoatrophic Mice.

ABSTRACT: Lipoatrophy is characterized as selective loss of adipose tissues, leading to the severity of cardiovascular disorders. Therefore, there was close intraorgan crosstalk between adipose tissue and cardiovascular in lipoatrophy. A-ZIP/F-1 mouse, a well-established lipoatrophic model, and primary cardiomyocytes were used for investigating the pathophysiological changes and molecular mechanisms. A-ZIP/F-1 mice had severe fat loss and impaired ventricular function during growth, but closely associated with the reduction of circulating vaspin levels. Administration of recombinant vaspin protein improved cardiac structural disorders, left ventricular dysfunction, and inflammatory response in lipoatrophic mice. In detail, vaspin decreased cardiac lipid deposits, but enhanced mitochondrial biogenesis and activities. Interestingly, A-ZIP/F-1 mice transplanted with normal visceral adipose tissues exhibited improvement in cardiac structural remodeling and mitochondrial function. Mechanistically, vaspin increased cardiac AKT activity, which guaranteed the mitochondrial benefits of vaspin in lipoatrophic mice and primary mouse cardiomyocytes. The present study suggested that vaspin possessed biological benefits in attenuating lipoatrophy-induced cardiomyopathy onset, and targeting vaspin/AKT signaling was a potential strategy to maintain heart metabolism.

SUBMITTER: Zhang D

PROVIDER: S-EPMC8497826 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Vaspin Mediates the Intraorgan Crosstalk Between Heart and Adipose Tissue in Lipoatrophic Mice.

Zhang Donghui D Zhu Hong H Zhan Enbo E Wang Fan F Liu Yue Y Xu Wei W Liu Xian X Liu Jingjin J Li Shufeng S Pan Yong Y Wang Yongshun Y Cao Wei W

Frontiers in cell and developmental biology 20210924

Lipoatrophy is characterized as selective loss of adipose tissues, leading to the severity of cardiovascular disorders. Therefore, there was close intraorgan crosstalk between adipose tissue and cardiovascular in lipoatrophy. A-ZIP/F-1 mouse, a well-established lipoatrophic model, and primary cardiomyocytes were used for investigating the pathophysiological changes and molecular mechanisms. A-ZIP/F-1 mice had severe fat loss and impaired ventricular function during growth, but closely associated ...[more]

PMID: 34631690

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Project description:Irisin is an exercise-induced hormone that regulates lipid metabolism. The present study investigates whether the anti-obesity effect of the natural flavonoid pentamethylquercetin (PMQ) is related to irisin secretion from skeletal muscle in whole animals and cultured cells. Obese mice induced by monosodium glutamate were administered oral PMQ to determine blood irisin level and in vivo parameters of lipid metabolism, and cultured mouse C2C12 myoblasts and 3T3-L1 preadipocytes were employed to investigate the related molecular identities. PMQ increased circulating irisin and decreased bodyweight, insulin, and lipid levels accompanied with increasing brown-like adipocyte formation in obese mice. The brown adipocyte marker uncoupling protein 1 (UCP-1) and other brown-like adipocyte-specific genes and/or markers were increased in mouse white fat tissue, while PMQ treatment reversed the above changes. PMQ also dose-dependently increased the reduced levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and fibronectin type III domain-containing 5 (FNDC5) signal molecules in obese mice. Interestingly, the irisin level was increased in the culture medium of C2C12 cells treated with PMQ, and the conditioned medium stimulated the brown-like transition of 3T3-L1 preadipocytes with the increased expression of PGC-1α, FNDC5, UCP-1, and other brown-like adipocyte-specific genes. The effects of conditioned culture medium were abolished in C2C12 cells with silenced PGC-1α. On the other hand, PMQ-induced upregulation of PGC-1α and FNDC5 expression was reduced by AMPK inhibitor Compound C in C2C12 cells. Our results demonstrate the novel information that PMQ-induced irisin secretion from skeletal muscle involves the improvement of metabolic dysfunction in obese mice via activating the AMPK/PGC-1α/FNDC5 signal pathway, suggesting that PMQ modulates skeletal muscle-adipose tissue crosstalk and may be a promising drug candidate for treating obesity and obesity-related metabolic diseases.

Dataset Information

Vaspin Mediates the Intraorgan Crosstalk Between Heart and Adipose Tissue in Lipoatrophic Mice.

Publications

Vaspin Mediates the Intraorgan Crosstalk Between Heart and Adipose Tissue in Lipoatrophic Mice.

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