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- W2110734560 abstract "Perilipin-1 (Plin1), exclusively located on the surface of lipid droplets in adipocytes, regulates the storage and hydrolysis of adipose triglycerides. Plin1 deficiency primarily causes low adiposity and aberrant lipolysis in rodents and humans. Here, we investigated whether adipose tissue dysfunction in perilipin-1 null (Plin1−/−) mice has maladaptive consequences for the heart and an association with hypertrophic cardiomyopathy. Perilipin-1 was expressed specifically in adipocytes but was undetectable in cardiomyocytes. Plin1−/− mice were histologically lipodystrophic, with reduced body fat. Paradoxically, the adipocytes of Plin1−/− mice, like those of obese and diabetic mammals, showed robust basal lipolysis and fatty acid efflux to the plasma. Such adipose tissue dysfunctions accounted for the ectopic lipid accumulation and enhanced fatty acid transport and oxidation in Plin1−/− mouse hearts. Excessive fatty acid β-oxidation and lipotoxicity induced excessive production of reactive oxygen species and oxidative stress because antioxidative capacity was reduced in cardiomyocytes, These malefactors injured the myocardial structure and function, as evidenced by disorganized myofilaments as well as irregular and swollen mitochondria with disrupted cristae. Finally, Plin1−/− mice showed grossly visible cardiac hypertrophy, with progressively up-regulated expression of hypertrophy and dysfunction marker genes, leading to heart failure, particularly with left ventricular diastolic dysfunction at 20 weeks of age. Adipose tissue dysfunction may have deleterious effects on the heart and contribute to the development of hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy in Plin1−/− mice with adipose tissue dysfunction may mimic and mechanistically explain the cardiomyopathies occurring in two typical adipose tissue disorders in humans, lipodystrophy and obesity." @default.
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- W2110734560 date "2014-11-21" @default.
- W2110734560 modified "2023-10-14" @default.
- W2110734560 title "Development of hypertrophic cardiomyopathy in perilipin-1 null mice with adipose tissue dysfunction" @default.
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- W2110734560 doi "https://doi.org/10.1093/cvr/cvu214" @default.
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