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  - Delgobo, Murilo
A1  - Heinrichs, Margarete
A1  - Hapke, Nils
A1  - Ashour, DiyaaElDin
A1  - Appel, Marc
A1  - Srivastava, Mugdha
A1  - Heckel, Tobias
A1  - Spyridopoulos, Ioakim
A1  - Hofmann, Ulrich
A1  - Frantz, Stefan
A1  - Ramos, Gustavo Campos
T1  - Terminally Differentiated CD4\(^+\) T Cells Promote Myocardial Inflammaging
JF  - Frontiers in Immunology
N2  - The cardiovascular and immune systems undergo profound and intertwined alterations with aging. Recent studies have reported that an accumulation of memory and terminally differentiated T cells in elderly subjects can fuel myocardial aging and boost the progression of heart diseases. Nevertheless, it remains unclear whether the immunological senescence profile is sufficient to cause age-related cardiac deterioration or merely acts as an amplifier of previous tissue-intrinsic damage. Herein, we sought to decompose the causality in this cardio-immune crosstalk by studying young mice harboring a senescent-like expanded CD4\(^+\) T cell compartment. Thus, immunodeficient NSG-DR1 mice expressing HLA-DRB1*01:01 were transplanted with human CD4\(^+\) T cells purified from matching donors that rapidly engrafted and expanded in the recipients without causing xenograft reactions. In the donor subjects, the CD4\(^+\) T cell compartment was primarily composed of naïve cells defined as CCR7\(^+\)CD45RO\(^-\). However, when transplanted into young lymphocyte-deficient mice, CD4\(^+\) T cells underwent homeostatic expansion, upregulated expression of PD-1 receptor and strongly shifted towards effector/memory (CCR7\(^-\) CD45RO\(^+\)) and terminally-differentiated phenotypes (CCR7\(^-\)CD45RO\(^-\)), as typically seen in elderly. Differentiated CD4\(^+\) T cells also infiltrated the myocardium of recipient mice at comparable levels to what is observed during physiological aging. In addition, young mice harboring an expanded CD4\(^+\) T cell compartment showed increased numbers of infiltrating monocytes, macrophages and dendritic cells in the heart. Bulk mRNA sequencing analyses further confirmed that expanding T-cells promote myocardial inflammaging, marked by a distinct age-related transcriptomic signature. Altogether, these data indicate that exaggerated CD4\(^+\) T-cell expansion and differentiation, a hallmark of the aging immune system, is sufficient to promote myocardial alterations compatible with inflammaging in juvenile healthy mice.
KW  - CD4+ T-cells
KW  - myocardial aging
KW  - inflammaging
KW  - NSG animals
KW  - immunosenescence
KW  - lymphocytes
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229612
SN  - 1664-3224
VL  - 12
ER  -