TY  - JOUR
A1  - Dischinger, Ulrich
A1  - Heckel, Tobias
A1  - Bischler, Thorsten
A1  - Hasinger, Julia
A1  - Königsrainer, Malina
A1  - Schmitt-Böhrer, Angelika
A1  - Otto, Christoph
A1  - Fassnacht, Martin
A1  - Seyfried, Florian
A1  - Hankir, Mohammed Khair
T1  - Roux-en-Y gastric bypass and caloric restriction but not gut hormone-based treatments profoundly impact the hypothalamic transcriptome in obese rats
JF  - Nutrients
N2  - Background: The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. Methods: Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1 mg/kg/day), liraglutide s.c. (0.4 mg/kg/day), PYY3-36 + liraglutide, and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA sequencing. Results: While rats in the RYGB, BWM, and PYY3-36 + liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK–STAT, PI3K-Akt, and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36 + liraglutide-, liraglutide-, and PYY-treated groups. Conclusions: Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36 + liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.
KW  - obesity
KW  - Roux-en-Y gastric bypass surgery
KW  - liraglutide
KW  - PYY3-36
KW  - hypothalamic gene expression
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252392
SN  - 2072-6643
VL  - 14
IS  - 1
ER  - 
TY  - JOUR
A1  - Veniaminova, Ekaterina
A1  - Cespuglio, Raymond
A1  - Chernukha, Irina
A1  - Schmitt-Boehrer, Angelika G.
A1  - Morozov, Sergey
A1  - Kalueff, Allan V.
A1  - Kuznetsova, Oxana
A1  - Anthony, Daniel C.
A1  - Lesch, Klaus-Peter
A1  - Strekalova, Tatyana
T1  - Metabolic, Molecular, and Behavioral Effects of Western Diet in Serotonin Transporter-Deficient Mice: Rescue by Heterozygosity?
JF  - Frontiers in Neuroscience
N2  - Reduced function of the serotonin transporter (SERT) is associated with increased susceptibility to anxiety and depression and with type-2 diabetes, which is especially true in older women. Preference for a “Western diet” (WD), enriched with saturated fat, cholesterol, and sugars, may aggravate these conditions. In previous studies, decreased glucose tolerance, central and peripheral inflammation, dyslipidemia, emotional, cognitive, and social abnormalities were reported in WD-fed young female mice. We investigated the metabolic, molecular, and behavioral changes associated with a 3-week-long dietary regime of either the WD or control diet in 12-month-old female mice with three different Sert genotypes: homozygous (Slc6a4) gene knockout (Sert\(^{−/−}\): KO), heterozygous (Sert\(^{+/−}\): HET), or wild-type mice (Sert\(^{+/+}\): WT). In the WT-WD and KO-WD groups, but not in HET-WD-fed mice, most of changes induced by the WD paralleled those found in the younger mice, including brain overexpression of inflammatory marker Toll-like receptor 4 (Tlr4) and impaired hippocampus-dependent performance in the marble test. However, the 12-month-old female mice became obese. Control diet KO mice exhibited impaired hippocampal-dependent behaviors, increased brain expression of the serotonin receptors Htr2c and Htr1b, as well as increased Tlr4 and mitochondrial regulator, peroxisome proliferator-activated receptor gamma-coactivator-1a (Ppargc1a). Paradoxically, these, and other changes, were reversed in KO-WD mutants, suggesting a complex interplay between Sert deficiency and metabolic factors as well as potential compensatory molecular mechanisms that might be disrupted by the WD exposure. Most, but not all, of the changes in gene expression in the brain and liver of KO mice were not exhibited by the HET mice fed with either diet. Some of the WD-induced changes were similar in the KO-WD and HET-WD-fed mice, but the latter displayed a “rescued” phenotype in terms of diet-induced abnormalities in glucose tolerance, neuroinflammation, and hippocampus-dependent performance. Thus, complete versus partial Sert inactivation in aged mice results in distinct metabolic, molecular, and behavioral consequences in response to the WD. Our findings show that Sert\(^{+/−}\) mice are resilient to certain environmental challenges and support the concept of heterosis as evolutionary adaptive mechanism.
KW  - Sert-deficient mice
KW  - Western diet
KW  - aging
KW  - glucose tolerance
KW  - Toll-like receptor 4 (TLR4)
KW  - serotonin receptors
KW  - obesity
KW  - heterosis
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199813
SN  - 1662-453X
VL  - 14
ER  -