Protective effects of sulforaphane on type 2 diabetes-induced cardiomyopathy via AMPK-mediated activation of lipid metabolic pathways and NRF2 function.
Metabolism
; 102: 154002, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31706979
ABSTRACT
BACKGROUND:
AMP-activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. It was reported that sulforaphane (SFN) prevented type 2 diabetes (T2D)-induced cardiomyopathy accompanied by the activation of AMPK; In this study, AMPK's pivotal role in SFN-mediated prevention against T2D-induced cardiomyopathy was tested using global deletion of AMPKα2 gene (AMPKα2-KO) mice. METHODS ANDRESULTS:
T2D was established by feeding 3-month high-fat diet (HFD) to induce insulin resistance, followed by an intraperitoneal injection of streptozotocin (STZ) to induce mild hyperglycemia in both AMPKα2-KO and wild-type (WT) mice. Then both T2D and control mice were subsequently treated with or without SFN for 3â¯months while continually feeding HFD or normal diet. Upon completion of the 3-month treatment, five mice from each group were sacrificed as a 3-month time-point (3â¯M). The rest continued normal diet or HFD until terminating study at the sixth month (6â¯M) of diabetes. Cardiac function was examined with echocardiography before sacrifice at both 3â¯M and 6â¯M. SFN prevented T2D-induced progression of cardiac dysfunction, remodeling (hypertrophy and fibrosis), inflammation, and oxidative damage in wild-type diabetic mice, but not in AMPKα2-KO mice. Mechanistically, SFN prevented T2D-induced cardiomyopathy not only by improving AMPK-mediated lipid metabolic pathways, but also enhancing NRF2 activation via AMPK/AKT/GSK3ß pathway. However, these improving effects of SFN were abolished in AMPKα2-KO diabetic mice.CONCLUSIONS:
AMPK is indispensable for the SFN-induced prevention of cardiomyopathy in T2D, and the activation of NRF2 by SFN is mediated by AMPK/AKT/GSK3ß signaling pathways.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cardiotónicos
/
Isotiocianatos
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Diabetes Mellitus Tipo 2
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Factor 2 Relacionado con NF-E2
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Cardiomiopatías Diabéticas
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Lipidosis
Límite:
Animals
Idioma:
En
Revista:
Metabolism
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos