Resum
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.
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.
| Idioma original | Anglès |
|---|---|
| Pàgines (de-a) | 2131-2145 |
| Nombre de pàgines | 15 |
| Revista | British Journal of Pharmacology |
| Volum | 178 |
| Número | 10 |
| DOIs | |
| Estat de la publicació | Publicada - de maig 2021 |
SDG de les Nacions Unides
Aquest resultat contribueix als següents objectius de desenvolupament sostenible.
