Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats

Mohammed K. Hankir, Florian Seyfried, Constantin A. Hintschich, Thi Ai Diep, Karen Kleberg, Mathias Kranz, Winnie Deuther-Conrad, Luis A. Tellez, Michael Rullmann, Marianne Patt, Jens Teichert, Swen Hesse, Osama Sabri, Peter Brust, Harald S. Hansen, Ivan E. de Araujo, Ute Krügel, Wiebke K. Fenske

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small intestine production of the fat-satiety molecule oleoylethanolamide (OEA). This was associated with vagus nerve-driven increases in dorsal striatal dopamine release. We also demonstrate that RYGB upregulates striatal dopamine 1 receptor (D1R) expression specifically under high-fat diet feeding conditions. Mechanistically, interfering with local OEA, vagal, and dorsal striatal D1R signaling negated the beneficial effects of RYGB on fat intake and preferences. These findings delineate a molecular/systems pathway through which bariatric surgery improves feeding behavior and may aid in the development of novel weight loss strategies that similarly modify brain reward circuits compromised in obesity.

Original languageEnglish
Pages (from-to)335-344
Number of pages10
JournalCell Metabolism
Volume25
Issue number2
DOIs
StatePublished - 7 Feb 2017
Externally publishedYes

Keywords

  • D1R signaling
  • OEA
  • PPAR-alpha
  • [11C] SCH 23390
  • altered nutrient preference
  • dopamine system
  • fat appetite
  • gastric bypass surgery

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