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Diet-Induced Obese Mice and Leptin-Deficient Lep ob/ob Mice Exhibit Increased Circulating GIP Levels Produced by Different Mechanisms.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Sep 10; Vol. 20 (18). Date of Electronic Publication: 2019 Sep 10. - Publication Year :
- 2019
-
Abstract
- As glucose-dependent insulinotropic polypeptide (GIP) possesses pro-adipogenic action, the suppression of the GIP hypersecretion seen in obesity might represent a novel therapeutic approach to the treatment of obesity. However, the mechanism of GIP hypersecretion remains largely unknown. In the present study, we investigated GIP secretion in two mouse models of obesity: High-fat diet-induced obese (DIO) mice and leptin-deficient Lep <superscript>ob/ob</superscript> mice. In DIO mice, plasma GIP was increased along with an increase in GIP mRNA expression in the lower small intestine. Despite the robust alteration in the gut microbiome in DIO mice, co-administration of maltose and the α-glucosidase inhibitor (α-GI) miglitol induced the microbiome-mediated suppression of GIP secretion. The plasma GIP levels of Lep <superscript>ob/ob</superscript> mice were also elevated and were suppressed by fat transplantation. The GIP mRNA expression in fat tissue was not increased in Lep <superscript>ob/ob</superscript> mice, while the expression of an interleukin-1 receptor antagonist (IL-1Ra) was increased. Fat transplantation suppressed the expression of IL-1Ra. The plasma IL-1Ra levels were positively correlated with the plasma GIP levels. Accordingly, although circulating GIP levels are increased in both DIO and Lep <superscript>ob/ob</superscript> mice, the underlying mechanisms differ, and the anti-obesity actions of α-GIs and leptin sensitizers may be mediated partly by the suppression of GIP secretion.
- Subjects :
- Animals
Gastric Inhibitory Polypeptide blood
Gastric Inhibitory Polypeptide genetics
Gene Expression
Interleukin 1 Receptor Antagonist Protein blood
Interleukin 1 Receptor Antagonist Protein genetics
Interleukin 1 Receptor Antagonist Protein metabolism
Leptin genetics
Male
Mice, Inbred C57BL
Mice, Obese
Obesity etiology
Obesity genetics
Receptors, G-Protein-Coupled genetics
Receptors, G-Protein-Coupled metabolism
Receptors, Gastrointestinal Hormone genetics
Receptors, Gastrointestinal Hormone metabolism
Diet, High-Fat adverse effects
Gastric Inhibitory Polypeptide metabolism
Leptin deficiency
Obesity metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31509948
- Full Text :
- https://doi.org/10.3390/ijms20184448