CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity.
Diabetes
; 70(2): 415-422, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33144338
ABSTRACT
Glucagon-like peptide 1 receptor (GLP-1R) agonists effectively improve glycemia and body weight in patients with type 2 diabetes and obesity but have limited weight-lowering efficacy and minimal insulin sensitizing action. In preclinical models, peripherally restricted cannabinoid receptor type 1 (CB1R) inhibitors, which are devoid of the neuropsychiatric adverse effects observed with brain-penetrant CB1R blockers, ameliorate obesity and its multiple metabolic complications. Using mouse models with genetic loss of CB1R or GLP-1R, we demonstrate that these two metabolic receptors modulate food intake and body weight via reciprocal functional interactions. In diet-induced obese mice, the coadministration of a peripheral CB1R inhibitor with long-acting GLP-1R agonists achieves greater reduction in body weight and fat mass than monotherapies by promoting negative energy balance. This cotreatment also results in larger improvements in systemic and hepatic insulin action, systemic dyslipidemia, and reduction of hepatic steatosis. Thus, peripheral CB1R blockade may allow safely potentiating the antiobesity and antidiabetic effects of currently available GLP-1R agonists.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peso Corporal
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Receptor CB1 de Canabinoide
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Ingestão de Alimentos
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Receptor do Peptídeo Semelhante ao Glucagon 1
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Obesidade
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França