Vascular effects of disrupting endothelial mTORC1 signaling in obesity.
Am J Physiol Regul Integr Comp Physiol
; 321(2): R228-R237, 2021 08 01.
Article
em En
| MEDLINE
| ID: mdl-34189960
ABSTRACT
The mechanistic target of rapamycin complex 1 (mTORC1) signaling complex is emerging as a critical regulator of cardiovascular function with alterations in this pathway implicated in cardiovascular diseases. In this study, we used animal models and human tissues to examine the role of vascular mTORC1 signaling in the endothelial dysfunction associated with obesity. In mice, obesity induced by high-fat/high-sucrose diet feeding for â¼2 mo resulted in aortic endothelial dysfunction without appreciable changes in vascular mTORC1 signaling. On the other hand, chronic high-fat diet feeding (45% or 60% kcal â¼9 mo) in mice resulted in endothelial dysfunction associated with elevated vascular mTORC1 signaling. Endothelial cells and visceral adipose vessels isolated from obese humans display a trend toward elevated mTORC1 signaling. Surprisingly, genetic disruption of endothelial mTORC1 signaling through constitutive or tamoxifen inducible deletion of endothelial Raptor (critical subunit of mTORC1) did not prevent or rescue the endothelial dysfunction associated with high-fat diet feeding in mice. Endothelial mTORC1 deficiency also failed to reverse the endothelial dysfunction evoked by a high-fat/high-sucrose diet in mice. Taken together, these data show increased vascular mTORC1 signaling in obesity, but this vascular mTORC1 activation appears not to be required for the development of endothelial impairment in obesity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
/
Endotélio Vascular
/
Gordura Subcutânea
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Alvo Mecanístico do Complexo 1 de Rapamicina
/
Obesidade
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Am J Physiol Regul Integr Comp Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article