Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.
Toxicol Lett
; 258: 134-146, 2016 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-27346292
ABSTRACT
Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities deficiency (ZD, 10mg zinc per 4057kcal), normal (ZN, 30mg zinc per 4057kcal) or supplement (ZS, 90mg zinc per 4057kcal). HFD induced a time-dependent obesity and ORCH, which was accompanied by increased cardiac inflammation and p38 MAPK activation. These effects were worsened by ZD in HFD/ZD mice and attenuated by ZS in HFD/ZS group, respectively. Also, administration of a p38 MAPK specific inhibitor in HFD mice for 3 months did not affect HFD-induced obesity, but completely abolished HFD-induced, and zinc deficiency-worsened, ORCH and cardiac inflammation. In vitro exposure of adult cardiomyocytes to palmitate induced cell hypertrophy accompanied by increased p38 MAPK activation, which was heightened by zinc depletion with its chelator TPEN. Inhibition of p38 MAPK with its specific siRNA also prevented the effects of palmitate on cardiomyocytes. These findings demonstrate that ZS alleviates but ZD heightens cardiac hypertrophy in HFD-induced obese mice through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Zinco
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Cardiomegalia
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Suplementos Nutricionais
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Sistema de Sinalização das MAP Quinases
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Deficiências Nutricionais
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Proteínas Quinases p38 Ativadas por Mitógeno
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Obesidade
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos