title: Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats.
abstract: Brain μ-opioid receptors (MORs) stimulate high-fat (HF) feeding and have been implicated in the distinct long term outcomes on body weight of bariatric surgery and dieting. Whether alterations in fat appetite specifically following these disparate weight loss interventions relate to changes in brain MOR signaling is unknown. To address this issue, diet-induced obese male rats underwent either Roux-en-Y gastric bypass (RYGB) or sham surgeries. Postoperatively, animals were placed on a two-choice diet consisting of low-fat (LF) and HF food and sham-operated rats were further split intoad libitumfed (Sham-LF/HF) and body weight-matched (Sham-BWM) to RYGB groups. An additional set of sham-operated rats always only on a LF diet (Sham-LF) served as lean controls, making four experimental groups in total. Corresponding to a stage of weight loss maintenance for RYGB rats, two-bottle fat preference tests in conjunction with small-animal positron emission tomography (PET) imaging studies with the selective MOR radioligand [11C]carfentanil were performed. Brains were subsequently collected and MOR protein levels in the hypothalamus, striatum, prefrontal cortex and orbitofrontal cortex were analyzed by Western Blot. We found that only the RYGB group presented with intervention-specific changes: having markedly suppressed intake and preference for high concentration fat emulsions, a widespread reduction in [11C]carfentanil binding potential (reflecting MOR availability) in various brain regions, and a downregulation of striatal and prefrontal MOR protein levels compared to the remaining groups. These findings suggest that the suppressed fat appetite caused by RYGB surgery is due to reduced brain MOR signaling, which may contribute to sustained weight loss unlike the case for dieting.
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of Leipzig Leipzig, Germany.
authors.forename: Mohammed K
authors.initials: MK
authors.lastname: Hankir
authors.affiliation: Department of Nuclear Medicine, University of Leipzig Leipzig, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Patt
authors.affiliation: Department of Nuclear Medicine, University of Leipzig Leipzig, Germany.
authors.forename: Jörg T W
authors.initials: JT
authors.lastname: Patt
authors.affiliation: Department of Nuclear Medicine, University of Leipzig Leipzig, Germany.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Becker
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of LeipzigLeipzig, Germany; Department of Nuclear Medicine, University of LeipzigLeipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rullmann
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig Leipzig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Kranz
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig Leipzig, Germany.
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of Leipzig Leipzig, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Schischke
authors.affiliation: Department of General and Visceral, Vascular and Paediatric Surgery, University of Würzburg Würzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Seyfried
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of LeipzigLeipzig, Germany; Department of Nuclear Medicine, University of LeipzigLeipzig, Germany.
authors.forename: Swen
authors.initials: S
authors.lastname: Hesse
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of LeipzigLeipzig, Germany; Department of Nuclear Medicine, University of LeipzigLeipzig, Germany.
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
authors.affiliation: Rudolf-Boehm Institute of Pharmacology and Toxicology, University of Leipzig Leipzig, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of Leipzig Leipzig, Germany.
authors.forename: Wiebke K
authors.initials: WK
authors.lastname: Fenske
keywords: Brain μ-opioid receptors; bariatric surgery; caloric-restriction; fat appetite; positron emission tomography imaging