TY  - JOUR
A1  - Hoffmann, Annett
A1  - Ebert, Thomas
A1  - Hankir, Mohammed K.
A1  - Flehmig, Gesine
A1  - Klöting, Nora
A1  - Jessnitzer, Beate
A1  - Lössner, Ulrike
A1  - Stumvoll, Michael
A1  - Blüher, Matthias
A1  - Fasshauer, Mathias
A1  - Tönjes, Anke
A1  - Miehle, Konstanze
A1  - Kralisch, Susan
T1  - Leptin improves parameters of brown adipose tissue thermogenesis in lipodystrophic mice
JF  - Nutrients
N2  - Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.
KW  - lipodystrophy
KW  - leptin
KW  - brown adipose tissue
KW  - thermogenesis
KW  - uncoupling protein 1
KW  - sympathetic nervous system
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242787
SN  - 2072-6643
VL  - 13
IS  - 8
ER  - 
TY  - JOUR
A1  - Griebsch, Nora-Isabell
A1  - Kern, Johanna
A1  - Hansen, Jonas
A1  - Rullmann, Michael
A1  - Luthardt, Julia
A1  - Helfmeyer, Stephanie
A1  - Dekorsy, Franziska J.
A1  - Soeder, Marvin
A1  - Hankir, Mohammed K.
A1  - Zientek, Franziska
A1  - Becker, Georg-Alexander
A1  - Patt, Marianne
A1  - Meyer, Philipp M.
A1  - Dietrich, Arne
A1  - Blüher, Matthias
A1  - Ding, Yu-Shin
A1  - Hilbert, Anja
A1  - Sabri, Osama
A1  - Hesse, Swen
T1  - Central serotonin/noradrenaline transporter availability and treatment success in patients with obesity
JF  - Brain Sciences
N2  - Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [\(^{11}\)C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [\(^{11}\)C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m\(^2\)) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.
KW  - obesity
KW  - serotonin
KW  - noradrenaline
KW  - serotonin transporter
KW  - noradrenaline transporter
KW  - Roux-en-Y gastric bypass surgery
KW  - body mass index (BMI; kg/m\(^2\))
KW  - radiotracer
KW  - PET
KW  - PET imaging
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290294
SN  - 2076-3425
VL  - 12
IS  - 11
ER  -