Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats

Sara Baidassano; Lwrke Smidt Gasbjerg; Husun Sheyma Kizilkaya; Mette Marie Rosenkilde; Jens Juul Holst; Bolette Hartmann

doi:10.3389/fendo.2019.00492

Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats

Sara Baidassano, Lwrke Smidt Gasbjerg, Husun Sheyma Kizilkaya, Mette Marie Rosenkilde, Jens Juul Holst, Bolette Hartmann

8 Citations (Scopus)

22 Downloads (Pure)

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of G protein-coupled receptors (R), the GIPR and GLP-2R, respectively. Both have been reported to influence metabolism. The purpose of the study was to investigate the role of the hormones in the regulation of lipid and bone homeostasis by subchronic treatment with novel GIPR and GLP-2R antagonists. Rats were injected once daily with vehicle, GIPR, or GLP-2R antagonists for 3 weeks. Body weight, food intake, body composition, plasma lipoprotein lipase (LPL), adipokines, triglycerides and the marker of bone resorption carboxy-terminal collagen crosslinks (CTX), were examined. In rats, subchronic treatment with GIPR antagonist, rat GIP (3-30)NH2, did not modify food intake and bone resorption, but significantly increased body weight, body fat mass, triglycerides, LPL, and leptin levels compared with vehicle treated rats. Subchronic (Pro3)GIP (a partial GIPR agonist), GLP-2(11-33), and GLP-2(3-33) (GLP-2R antagonists) treatment did not affect any parameter. The present results would be consistent with a role for GIP, but not GLP-2, in the maintenance of lipid homeostasis in rats, while neither GIPR nor GLP-2R antagonism appeared to influence bone resorption in rats.

Original language	English
Article number	492
Journal	Frontiers in Endocrinology
Volume	10
Number of pages	11
ISSN	1664-2392
DOIs	https://doi.org/10.3389/fendo.2019.00492
Publication status	Published - 2019

Keywords

glucose-dependent insulinotropic polypeptide (GIP)
GIP receptor
GIP receptor antagonist
glucagon-like peptide-2 (GLP-2)
lipid homeostasis

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Cite this

@article{a2f11b0753104a58bbf1791e6d94e78b,

title = "Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats",

abstract = "Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of G protein-coupled receptors (R), the GIPR and GLP-2R, respectively. Both have been reported to influence metabolism. The purpose of the study was to investigate the role of the hormones in the regulation of lipid and bone homeostasis by subchronic treatment with novel GIPR and GLP-2R antagonists. Rats were injected once daily with vehicle, GIPR, or GLP-2R antagonists for 3 weeks. Body weight, food intake, body composition, plasma lipoprotein lipase (LPL), adipokines, triglycerides and the marker of bone resorption carboxy-terminal collagen crosslinks (CTX), were examined. In rats, subchronic treatment with GIPR antagonist, rat GIP (3-30)NH2, did not modify food intake and bone resorption, but significantly increased body weight, body fat mass, triglycerides, LPL, and leptin levels compared with vehicle treated rats. Subchronic (Pro3)GIP (a partial GIPR agonist), GLP-2(11-33), and GLP-2(3-33) (GLP-2R antagonists) treatment did not affect any parameter. The present results would be consistent with a role for GIP, but not GLP-2, in the maintenance of lipid homeostasis in rats, while neither GIPR nor GLP-2R antagonism appeared to influence bone resorption in rats.",

keywords = "glucose-dependent insulinotropic polypeptide (GIP), GIP receptor, GIP receptor antagonist, glucagon-like peptide-2 (GLP-2), lipid homeostasis",

author = "Sara Baidassano and Gasbjerg, {Lwrke Smidt} and Kizilkaya, {Husun Sheyma} and Rosenkilde, {Mette Marie} and Holst, {Jens Juul} and Bolette Hartmann",

year = "2019",

doi = "10.3389/fendo.2019.00492",

language = "English",

volume = "10",

journal = "Frontiers in Endocrinology",

issn = "1664-2392",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats

AU - Baidassano, Sara

AU - Gasbjerg, Lwrke Smidt

AU - Kizilkaya, Husun Sheyma

AU - Rosenkilde, Mette Marie

AU - Holst, Jens Juul

AU - Hartmann, Bolette

PY - 2019

Y1 - 2019

N2 - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of G protein-coupled receptors (R), the GIPR and GLP-2R, respectively. Both have been reported to influence metabolism. The purpose of the study was to investigate the role of the hormones in the regulation of lipid and bone homeostasis by subchronic treatment with novel GIPR and GLP-2R antagonists. Rats were injected once daily with vehicle, GIPR, or GLP-2R antagonists for 3 weeks. Body weight, food intake, body composition, plasma lipoprotein lipase (LPL), adipokines, triglycerides and the marker of bone resorption carboxy-terminal collagen crosslinks (CTX), were examined. In rats, subchronic treatment with GIPR antagonist, rat GIP (3-30)NH2, did not modify food intake and bone resorption, but significantly increased body weight, body fat mass, triglycerides, LPL, and leptin levels compared with vehicle treated rats. Subchronic (Pro3)GIP (a partial GIPR agonist), GLP-2(11-33), and GLP-2(3-33) (GLP-2R antagonists) treatment did not affect any parameter. The present results would be consistent with a role for GIP, but not GLP-2, in the maintenance of lipid homeostasis in rats, while neither GIPR nor GLP-2R antagonism appeared to influence bone resorption in rats.

AB - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of G protein-coupled receptors (R), the GIPR and GLP-2R, respectively. Both have been reported to influence metabolism. The purpose of the study was to investigate the role of the hormones in the regulation of lipid and bone homeostasis by subchronic treatment with novel GIPR and GLP-2R antagonists. Rats were injected once daily with vehicle, GIPR, or GLP-2R antagonists for 3 weeks. Body weight, food intake, body composition, plasma lipoprotein lipase (LPL), adipokines, triglycerides and the marker of bone resorption carboxy-terminal collagen crosslinks (CTX), were examined. In rats, subchronic treatment with GIPR antagonist, rat GIP (3-30)NH2, did not modify food intake and bone resorption, but significantly increased body weight, body fat mass, triglycerides, LPL, and leptin levels compared with vehicle treated rats. Subchronic (Pro3)GIP (a partial GIPR agonist), GLP-2(11-33), and GLP-2(3-33) (GLP-2R antagonists) treatment did not affect any parameter. The present results would be consistent with a role for GIP, but not GLP-2, in the maintenance of lipid homeostasis in rats, while neither GIPR nor GLP-2R antagonism appeared to influence bone resorption in rats.

KW - glucose-dependent insulinotropic polypeptide (GIP)

KW - GIP receptor

KW - GIP receptor antagonist

KW - glucagon-like peptide-2 (GLP-2)

KW - lipid homeostasis

U2 - 10.3389/fendo.2019.00492

DO - 10.3389/fendo.2019.00492

M3 - Journal article

C2 - 31447774

SN - 1664-2392

VL - 10

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 492

ER -