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  - Popp, Sandy
A1  - Schmitt-Böhrer, Angelika
A1  - Langer, Simon
A1  - Hofmann, Ulrich
A1  - Hommers, Leif
A1  - Schuh, Kai
A1  - Frantz, Stefan
A1  - Lesch, Klaus-Peter
A1  - Frey, Anna
T1  - 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
JF  - Journal of Clinical Medicine
N2  - Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
KW  - chronic heart failure
KW  - myocardial infarction
KW  - serotonin transporter deficient mice
KW  - anxiety
KW  - depression
KW  - behavior
KW  - inflammation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242739
SN  - 2077-0383
VL  - 10
IS  - 14
ER  -