Adipocyte-specific expression of a retinoic acid receptor α dominant negative form causes glucose intolerance and hepatic steatosis in mice.
Biochem Biophys Res Commun
; 514(4): 1231-1237, 2019 07 05.
Article
em En
| MEDLINE
| ID: mdl-31109648
ABSTRACT
All-trans-retinoic acid (ATRA) has been well described as a positive regulator for early stage of adipocyte differentiation and lipid metabolism and also linked to an in vivo fat-lowering effect in mice. However, not all studies support this association. Our objective was to characterize the action of ATRA in mature adipocytes of mice by ablating RAR signaling through overexpression of a well-characterized dominant negative RARα mutant (RARdn) form specifically in adipocytes. Altered RAR signaling in adipocytes resulted in a significant decrease in ATRA levels in visceral and brown adipose tissues as well as liver tissue. This was linked to significant impairments in glucose clearance and elevated hepatic lipid accumulation for chow diet fed mice, indicating the development of metabolic disease, including hepatic steatosis. In addition, we found that adipose RARdn expression in mice fed a chow diet decreased thermogenesis. We conclude that altered RAR signaling and ATRA levels in adipocytes impacts glucose and lipid metabolism in mice.
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Base de dados:
MEDLINE
Assunto principal:
Intolerância à Glucose
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Adipócitos
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Fígado Gorduroso
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Receptor alfa de Ácido Retinoico
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article