TY  - JOUR
A1  - Pfeiffer, Susanne
A1  - Krüger, Jacqueline
A1  - Maierhofer, Anna
A1  - Böttcher, Yvonne
A1  - Klöting, Nora
A1  - El Hajj, Nady
A1  - Schleinitz, Dorit
A1  - Schön, Michael R.
A1  - Dietrich, Arne
A1  - Fasshauer, Mathias
A1  - Lohmann, Tobias
A1  - Dreßler, Miriam
A1  - Stumvoll, Michael
A1  - Haaf, Thomas
A1  - Blüher, Matthias
A1  - Kovacs, Peter
T1  - Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction
JF  - Scientific Reports
N2  - Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits. In subgroups of individuals, we investigated the effects on HIF3A genetic variants on its AT expression (N = 603) and methylation of CpG-sites (N = 87). HIF3A expression was significantly higher in SAT compared to VAT and correlated with obesity and parameters of AT dysfunction (including CRP and leucocytes count). HIF3A methylation at cg22891070 was significantly higher in VAT compared to SAT and correlated with BMI, abdominal SAT and VAT area. Rs8102595 showed a nominal significant association with AT HIF3A methylation levels as well as with obesity and fat distribution. HIF3A expression and methylation in AT are fat depot specific, related to obesity and AT dysfunction. Our data support the hypothesis that HIF pathways may play an important role in the development of AT dysfunction in obesity.
KW  - gene expression
KW  - adipose
KW  - hypoxia-inducible factor 3A
KW  - adipose tissue dysfunction
KW  - obesity
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167662
VL  - 6
IS  - 27969
ER  - 
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  -