Impaired GLP-1 signaling contributes to reduced sensitivity to duodenal nutrients in obesity-prone rats during high-fat feeding

Frank A. Duca, Shahbaz Katebzadeh, Mihai Covasa

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Objective Increased consumption of a high-fat (HF) diet is a salient contributor to obesity; however, how diminished satiation signaling contributes to overconsumption and obesity development remains poorly understood. Methods Using obese-prone (OP) and obese-resistant (OR) rats, we tested feeding responses to intragastric liquid meal replacement, prior and after HF feeding. Next, chow- and HF-fed OP and OR rats were tested for sensitivity to intraduodenal glucose, intralipid, and meal replacement loads. To examine the role of glucagon-like peptide-1 (GLP-1) and vagal signaling, animals were treated with exendin-9, GLP-1 receptor antagonist, prior to meal replacement infusion, and Fos-like immunoreactivity (Fos-Li) in the dorsal hindbrain was examined after infusion. Results OP and OR rats reduced chow intake equally following gastric liquid meal; however, after 2 weeks of HF feeding, intragastric meal replacement reduced food intake less in OP than OR. Similarly, HF feeding, but not chow, diminished the suppressive effects of intraduodenal meal replacement, glucose, and intralipid in OP compared to OR. This effect was associated with lower Fos-Li expression in the dorsal hindbrain of OP rats. Finally, exendin-9 failed to attenuate reduction of food intake by meal replacement in OP rats during HF feeding. Conclusions Susceptibility to obesity coupled with HF feeding results in rapid impairments in nutrient-induced satiation through blunted responses in endogenous GLP-1 and hindbrain vagal afferent signaling.

Original languageEnglish (US)
Pages (from-to)2260-2268
Number of pages9
JournalObesity
Volume23
Issue number11
DOIs
StatePublished - Nov 2015

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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