Combination of obesity and high-Fat feeding diminishes sensitivity to GLP-1R agonist exendin-4

Frank A. Duca, Yassine Sakar, Mihai Covasa

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Gastrointestinal mechanisms involved in the suppression of appetite are compromised in obesity. Glucagon-like peptide-1 (GLP-1) is released in response to nutrients, suppresses food intake, and has been shown to play a role in regulation of energy balance. It is not known whether obese-prone (OP) rats exhibit dysfunctional GLP-1 signaling that could contribute to decreased nutrient-induced satiation and hyperphagia. Therefore, we examined the effects of exogenous intraperitoneal administration of the GLP-1R agonist, exendin-4 (Ex-4), on food intake in OP and obese-resistant (OR) rats during chow or high-energy/high-fat (HE/HF) feeding. All doses of Ex-4 effectively suppressed intake in OP and OR rats fed chow; however, during HE/HF-feeding, OP rats suppressed intake significantly less than OR rats at all Ex-4 doses tested. This was associated with downregulation of GLP-1R mRNA expression in the vagal nodose ganglia of OP rats. Furthermore, HE/HF-fed OP rats had significantly lower plasma GLP-1 levels, decreased protein levels of GLP-1 in the intestinal epithelium, and reduced number of L cells in the distal ileum. These results demonstrate that HE/HF-feeding, coupled with OP phenotype, results in reduced endogenous GLP-1 and GLP-1R activation, indicating that impaired GLP-1 signaling during obesity may exacerbate hyperphagia and weight gain.

Original languageEnglish (US)
Pages (from-to)2410-2415
Number of pages6
JournalDiabetes
Volume62
Issue number7
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Fingerprint

Glucagon-Like Peptide 1
Obesity
Fats
Hyperphagia
Eating
Nodose Ganglion
Satiation
Food
Appetite
Intestinal Mucosa
exenatide
Ileum
Weight Gain
Down-Regulation
Cell Count
Phenotype
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Combination of obesity and high-Fat feeding diminishes sensitivity to GLP-1R agonist exendin-4. / Duca, Frank A.; Sakar, Yassine; Covasa, Mihai.

In: Diabetes, Vol. 62, No. 7, 01.07.2013, p. 2410-2415.

Research output: Contribution to journalArticle

Duca, Frank A. ; Sakar, Yassine ; Covasa, Mihai. / Combination of obesity and high-Fat feeding diminishes sensitivity to GLP-1R agonist exendin-4. In: Diabetes. 2013 ; Vol. 62, No. 7. pp. 2410-2415.
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