University: Universitat Leipzig, University of Wurzburg, University of Copenhagen, Yale University
Authors: 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
Journal: Cell Metabolism
Impact Factor: 21.567 (What is the IF?).
TITLE: Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats
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.