Author, as appears in the article.: Ejarque, Miriam; Sabadell-Basallote, Joan; Beiroa, Daniel; Calvo, Enrique; Keiran, Noelia; Nunez-Roa, Catalina; Rodriguez, Maria del Mar; Sabench, Fatima; del Castillo, Daniel; Jimenez, Veronica; Bosch, Fatima; Nogueiras, Ruben; Vendrell, Joan; Fernandez-Veledo, Sonia;

Department: Ciències Mèdiques Bàsiques Medicina i Cirurgia Bioquímica i Biotecnologia

URV's Author/s: Del Castillo Déjardin, Daniel / Fernandez Veledo, Sonia / Sabench Pereferrer, Fàtima / Vendrell Ortega, Juan José

Keywords: Teduglutide Short-bowel syndrome Protein-coupled receptor Pharmacology Obesity Obese mice Nervous-system Inflammatory Inflammation In-vivo Glucagon-like peptide-2 Glp‐ Glp-2 Concise guide Anti‐ Anti-inflammatory Adipose tissue 2

Abstract: Background and Purpose Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone released in response to nutritional intake that exerts a wide range of effects by activating GLP-2 receptors. In addition to its intestinotrophic effects, GLP-2 also positively influences glucose metabolism under conditions of obesity, but the mechanisms behind this remain unclear. Here, we have investigated the molecular role of the GLP-2/GLP-2 receptor axis in energetic metabolism, focusing on its potential modulatory effects on adipose tissue. Experimental Approach Physiological measurements (body weight, food intake, locomotor activity, and energy expenditure) and metabolic studies (glucose and insulin tolerance tests) were performed on lean and obese mice treated with the protease-resistant GLP-2 analogue teduglutide. Key Results Acute but not chronic centrally administered teduglutide decreased food intake and weight-gain. By contrast, chronic activation of peripheral GLP-2 receptors increased body weight-independent glucose tolerance and had anti-inflammatory effects on visceral adipose tissue. Using a gene silencing approach, we found that adipose tissue is necessary for these beneficial effects of teduglutide. Finally, teduglutide regulates the inflammatory state and acts as an anabolic signal in human adipocytes. Conclusion and Implications Overall, our data identify adipose tissue as a new, clinically relevant, site of action for GLP-2 activity in obesity.

Thematic Areas: Saúde coletiva Química Psicología Pharmacology & pharmacy Pharmacology Odontología Nutrição Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Ensino Engenharias iv Engenharias ii Enfermagem Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biodiversidade Biochemistry & molecular biology Astronomia / física

Author's mail: sonia.fernandez@urv.cat danieldel.castillo@urv.cat juanjose.vendrell@urv.cat fatima.sabench@urv.cat

Author identifier: 0000-0003-2906-3788 0000-0003-0456-3102 0000-0001-7024-7824 0000-0002-6994-6115 0000-0002-9262-8756

Record's date: 2023-02-23

Papper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.15278

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: British Journal Of Pharmacology. 178 (10): 2131-2145

APA: Ejarque, Miriam; Sabadell-Basallote, Joan; Beiroa, Daniel; Calvo, Enrique; Keiran, Noelia; Nunez-Roa, Catalina; Rodriguez, Maria del Mar; Sabench, Fat (2021). Adipose tissue is a key organ for the beneficial effects of GLP-2 metabolic function. British Journal Of Pharmacology, 178(10), 2131-2145. DOI: 10.1111/bph.15278

Article's DOI: 10.1111/bph.15278

Entity: Universitat Rovira i Virgili

Journal publication year: 2021

Publication Type: Journal Publications