TY  - JOUR
A1  - Hankir, Mohammed K.
A1  - Patt, Marianne
A1  - Patt, Jörg T. W.
A1  - Becker, Georg A.
A1  - Rullmann, Michael
A1  - Kranz, Mathias
A1  - Deuther-Conrad, Winnie
A1  - Schischke, Kristin
A1  - Seyfried, Florian
A1  - Brust, Peter
A1  - Hesse, Swen
A1  - Sabri, Osama
A1  - Krügel, Ute
A1  - Fenske, Wiebke
T1  - Suppressed fat appetite after Roux-en-Y gastric bypass surgery associates with reduced brain mu-opioid receptor availability in diet-induced obese male rats
JF  - Frontiers in Neuroscience
N2  - 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 into ad libitum fed (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 [\(^{11}\)C]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 [\(^{11}\)C]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.
KW  - bariatric surgery
KW  - caloric-restriction
KW  - fat appetite
KW  - Brain μ-opioid receptors
KW  - positron emission tomography imaging
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181130
VL  - 10
ER  - 
TY  - JOUR
A1  - Refardt, Julie
A1  - Sailer, Clara Odilia
A1  - Winzeler, Bettina
A1  - Betz, Matthias Johannes
A1  - Chifu, Irina
A1  - Schnyder, Ingeborg
A1  - Fassnacht, Martin
A1  - Fenske, Wiebke
A1  - Christ-Crain, Mirjam
T1  - FGF-21 levels in polyuria-polydipsia syndrome
JF  - Endocrine Connections
N2  - The pathomechanism of primary polydipsia is poorly understood. Recent animal data reported a connection between fibroblast growth factor 21 (FGF-21) and elevated fluid intake independently of hormonal control by the hormone arginine-vasopressin (AVP) and osmotic stimulation. We therefore compared circulating FGF-21 levels in patients with primary polydipsia to patients with AVP deficiency (central diabetes insipidus) and healthy volunteers. In this prospective cohort study, we analyzed FGF-21 levels of 20 patients with primary polydipsia, 20 patients with central diabetes insipidus and 20 healthy volunteers before and after stimulation with hypertonic saline infusion targeting a plasma sodium level >= 150 mmol/L. The primary outcome was the difference in FGF-21 levels between the three groups. Baseline characteristics were similar between the groups except for patients with central diabetes insipidus being heavier. There was no difference in baseline FGF-21 levels between patients with primary polydipsia and healthy volunteers (122 pg/mL (52,277) vs 193 pg/mL (48,301), but higher levels in patients with central diabetes insipidus were observed (306 pg/mL (114,484); P=0.037). However, this was not confirmed in a multivariate linear regression analysis after adjusting for age, sex, BMI and smoking status. Osmotic stimulation did not affect FGF-21 levels in either group (difference to baseline: primary polydipsia -23 pg/mL (-43, 22); central diabetes insipidus 17 pg/mL (-76, 88); healthy volunteers -6 pg/mL (-68, 22); P=0.45). To conclude, FGF-21 levels are not increased in patients with primary polydipsia as compared to central diabetes insipidus or healthy volunteers. FGF-21 therefore does not seem to be causal of elevated fluid intake in these patients.
KW  - FGF21
KW  - diabetes insipidus
KW  - primary polydipsia
KW  - osmotic stimulation
KW  - copeptin
KW  - Fibroblast Growth Factor-21
KW  - Klotho-related molecules
KW  - Copeptin
KW  - Diagnosis
KW  - PF-05231023
KW  - Resistance
KW  - Men
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225085
VL  - 7
IS  - 12
ER  -