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• W2768210859 abstract "Abstract Aim To explore the cooperation of GLP ‐1 receptor and β3‐adrenergic receptor (β3‐ AR )‐mediated signalling in the control of fat mass/feeding behaviour by studying the effects of a combined therapy composed of the GLP ‐1R agonist liraglutide and the β3‐ AR agonist CL 316243. Methods The study included the analysis of key mechanisms regulating lipid/cholesterol metabolism, and thermogenesis in brown ( BAT ) and epididymal white ( eWAT ) adipose tissues, abdominal muscle and liver of male rats. Results CL 316243 (1 mg kg −1 ) and liraglutide (100 μg kg −1 ) co‐administration over 6 days potentiated an overall negative energy balance (reduction in food intake, body weight gain, fat/non‐fat mass ratio, liver fat content, and circulating levels of non‐essential fatty acids, triglycerides, very low‐density lipoprotein‐cholesterol and leptin). These effects were accompanied by increased plasma levels of insulin and IL 6. We also observed increased gene expression of uncoupling proteins regulating thermogenesis in BAT / eWAT ( Ucp1 ) and muscle ( Ucp2/3 ). Expression of transcription factor and enzymes involved either in de novo lipogenesis ( Chrebp , Acaca , Fasn , Scd1 , Insig1 , Srebp1 ) or in fatty acid β‐oxidation ( Cpt1b ) was enhanced in eWAT and/or muscle but decreased in BAT . Ppar α and Ppar γ, essentials in lipid flux/storage, were decreased in BAT / eWAT but increased in the muscle and liver. Cholesterol synthesis regulators ( Insig2 , Srebp2 , Hmgcr ) were particularly over‐expressed in muscle. These GLP ‐1R/β3‐ AR ‐induced metabolic effects were associated with the downregulation of cAMP ‐dependent signalling pathways ( PKA / AKT /AMPK). Conclusion Combined activation of GLP ‐1 and β3‐ AR s potentiate changes in peripheral pathways regulating lipid/cholesterol metabolism in a tissue‐specific manner that favours a switch in energy availability/expenditure and may be useful for obesity treatment." @default.
• W2768210859 created "2017-12-04" @default.
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• W2768210859 date "2017-12-19" @default.
• W2768210859 modified "2023-10-17" @default.
• W2768210859 title "Cooperative role of the glucagon-like peptide-1 receptor and β3-adrenergic-mediated signalling on fat mass reduction through the downregulation of PKA/AKT/AMPK signalling in the adipose tissue and muscle of rats" @default.
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• W2768210859 doi "https://doi.org/10.1111/apha.13008" @default.
• W2768210859 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29193738" @default.
• W2768210859 hasPublicationYear "2017" @default.
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