Angiotensin-(1-7), the product of ACE2 ameliorates NAFLD by acting through its receptor Mas to regulate hepatic mitochondrial function and glycolipid metabolism.
FASEB J
; 34(12): 16291-16306, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33078906
ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is the most general liver disease characterized by a continuum of liver abnormalities ranging from simple fatty liver to advanced stage of nonalcoholic steatohepatitis, cirrhosis, and even hepatocellular carcinoma. The pathological drivers of NAFLD are complex and largely undefined. It is increasingly identified that the imbalance between renin-angiotensin system and ACE2/Ang-(1-7)/Mas axis, as well as mitochondrial dysfunction associated with NAFLD. However, no known empirical research has focused on exploring the effect of the regulation of mitochondrial respiration chain activity by Ang-(1-7)/Mas on the prevention of NAFLD. Here, we evaluated the interaction and relevance of hepatic Ang-(1-7)/Mas-axis challenge with glucolipid metabolism and mitochondrial condition in vivo and in vitro. In this context, we found that Mas deletion in mice contributed to the severe glucose intolerance, insulin resistance, and hepatic steatosis which accompanied by elevated levels of serum/ hepatic alanine aminotransferase, aspartate aminotransferase, and triglycerides, as well as the mitochondrial dysfunction. Whereas forced upregulation of Mas or Ang-(1-7) administration could significantly attenuate these consequences by downregulating the expression of hepatic lipogenic proteins and enzymes for gluconeogenesis. Furthermore, activation of Ang-(1-7)/Mas arm could improve the IRS-1/Akt/AMPK pathway and enhance the mitochondrial energy utilization. Considered together, it is becoming extremely hopeful to provide a new perspective for Ang-(1-7)/Mas axis for the therapeutics of NAFLD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Angiotensina I
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Glicolipídeos
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Proteínas Proto-Oncogênicas
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Receptores Acoplados a Proteínas G
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Hepatopatia Gordurosa não Alcoólica
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Enzima de Conversão de Angiotensina 2
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Fígado
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Mitocôndrias
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
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FISIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China