CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity. / Zizzari, Philippe; He, Rongjun; Falk, Sarah; Bellocchio, Luigi; Allard, Camille; Clark, Samantha; Lesté-Lasserre, Thierry; Marsicano, Giovanni; Clemmensen, Christoffer; Perez-Tilve, Diego; Finan, Brian; Cota, Daniela; Quarta, Carmelo.

In: Diabetes, Vol. 70, No. 2, 2021, p. 415-422.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zizzari, P, He, R, Falk, S, Bellocchio, L, Allard, C, Clark, S, Lesté-Lasserre, T, Marsicano, G, Clemmensen, C, Perez-Tilve, D, Finan, B, Cota, D & Quarta, C 2021, 'CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity', Diabetes, vol. 70, no. 2, pp. 415-422. https://doi.org/10.2337/db20-0162

APA

Zizzari, P., He, R., Falk, S., Bellocchio, L., Allard, C., Clark, S., Lesté-Lasserre, T., Marsicano, G., Clemmensen, C., Perez-Tilve, D., Finan, B., Cota, D., & Quarta, C. (2021). CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity. Diabetes, 70(2), 415-422. https://doi.org/10.2337/db20-0162

Vancouver

Zizzari P, He R, Falk S, Bellocchio L, Allard C, Clark S et al. CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity. Diabetes. 2021;70(2):415-422. https://doi.org/10.2337/db20-0162

Author

Zizzari, Philippe ; He, Rongjun ; Falk, Sarah ; Bellocchio, Luigi ; Allard, Camille ; Clark, Samantha ; Lesté-Lasserre, Thierry ; Marsicano, Giovanni ; Clemmensen, Christoffer ; Perez-Tilve, Diego ; Finan, Brian ; Cota, Daniela ; Quarta, Carmelo. / CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity. In: Diabetes. 2021 ; Vol. 70, No. 2. pp. 415-422.

Bibtex

@article{07909c01623a42ff9a1281675cd45b13,
title = "CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity",
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.",
author = "Philippe Zizzari and Rongjun He and Sarah Falk and Luigi Bellocchio and Camille Allard and Samantha Clark and Thierry Lest{\'e}-Lasserre and Giovanni Marsicano and Christoffer Clemmensen and Diego Perez-Tilve and Brian Finan and Daniela Cota and Carmelo Quarta",
year = "2021",
doi = "10.2337/db20-0162",
language = "English",
volume = "70",
pages = "415--422",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "2",

}

RIS

TY - JOUR

T1 - CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity

AU - Zizzari, Philippe

AU - He, Rongjun

AU - Falk, Sarah

AU - Bellocchio, Luigi

AU - Allard, Camille

AU - Clark, Samantha

AU - Lesté-Lasserre, Thierry

AU - Marsicano, Giovanni

AU - Clemmensen, Christoffer

AU - Perez-Tilve, Diego

AU - Finan, Brian

AU - Cota, Daniela

AU - Quarta, Carmelo

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.2337/db20-0162

DO - 10.2337/db20-0162

M3 - Journal article

C2 - 33144338

AN - SCOPUS:85100280324

VL - 70

SP - 415

EP - 422

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 2

ER -

ID: 256516453