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

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

  • 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
  • Hansen, Harald S.
  • Ivan E de Araujo
  • Ute Krügel
  • Wiebke K Fenske

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.

OriginalsprogEngelsk
TidsskriftCell Metabolism
Vol/bind25
Udgave nummer2
Sider (fra-til)335-344
Antal sider10
ISSN1550-4131
DOI
StatusUdgivet - 7 feb. 2017

ID: 174431099