Exploring obesity with respect to the mTOR pathway and its regulating micro-RNAs and to epigenetic changes in the methylation pattern of obesity associated genes
Gastroenterology
Human Genetics
Final Report Abstract
In this application, the importance of bariatric surgery for the expression of genes in the metabolic pathway of mTOR in the context of obesity was studied. The mammalian/ mechanistic target of rapamycin (mTOR) is known as a key element of crucial regulatory pathways and a modulator of metabolic processes. Mediated by its downstream target p70S6K, mTOR induces glycolysis, protein synthesis, adipo- and lipogenesis. Gene expression was monitored in peripheral blood mononuclear cells from 22 adipose patients and 20 healthy controls by qRT-PCR after isolating mRNA and synthesizing cDNA. mTORC1 (mTOR & p70S6K) and mTORC2 (AKT) gene expressions were investigated by qRT-PCR in adipose patients pre- and postoperatively and in a control cohort. All data were also confirmed by protein analysis. Preoperatively, mTOR and p70S6K mRNA expression were revealed to be significantly elevated in adipose patients in comparison to the normal weight control cohort. mTORC1 gene expression correlated positively with weight and BMI. This was not the case for AKT. Directly after bariatric surgery in the postoperative days, a significant decrease of mTOR and p70S6K mRNA expression was monitored. In the following postoperative three and six months, gene expression from mTORC1 remained significantly reduced and resembled the gene expression levels of the normal-weight control subjects. On the one hand, being a component of mTORC2, AKT serves as an antagonist to mTORC1, while on the other hand, AKT also serves as an upstream target of mTORC1 as a direct inductor. 12 months postoperatively, gene expression at the mRNA level of the three target genes increased back to the original expression levels. Postoperatively, about 75% of included patients with T2DM showed significant remission of T2DM. All patients with T2DM and arterial hypertension were able to reduce their medication after bariatric surgery. Bariatric intervention might reverse the dysregulation of the mTOR pathway in insulin resistance through decreased mTORC1 gene expression. Obesity and T2DM significantly increase mRNA expression of mTOR and p70S6K to inhibit the insulin-receptor-substrate at the cell membrane. Long-time inhibition could lead to insulin resistance. Reduced mTORC1 gene expression might decrease this inhibition and subsequently diminish insulin resistance postoperatively. Therefore, the mTOR-pathway plays an important role in the context of understanding the development and therapy of metabolic diseases such as obesity and T2DM.
Publications
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Bariatric surgery counteracts insulin dependency of adipose patients under the simultaneous significant reduction of mTOR gene expression. In Innovative Surgical Sciences 6 (Special Suppl 1): S1–S80
I. Schwörer, C. Rubie, L-K. Feiner, S. Holländer & M. Glanemann
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Deutschen Chirurgenkongress 2021 (DGCH Annual Congress 2021): I. Schwörer, C. Rubie, L-K. Feiner, S. Holländer, M. Glanemann. Bariatric surgery counteracts insulin dependency of adipose patients under the simultaneous significant reduction of mTOR gene expression
I. Schwörer, C. Rubie, L-K. Feiner, S. Holländer & M. Glanemann
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Einfluss bariatrischer Chirurgie auf die Insulinabhängigkeit adipöser Patienten und auf die Expression von Genen des mTOR-Signalweges. Mittelrheiner 12.10.2023 – 13.10.2023
Laura Kim Feiner, Isabella Schwörer, Sebastian Holländer, Matthias Glanemann & Claudia Rubie
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Bariatric surgery counteracts insulin dependency of adipose patients under the simultaneous significant reduction of mTOR gene expression. DCK 16.04.2024 – 18.04.2024
Laura Kim Feiner, Isabella Schwörer, Sebastian Holländer, Matthias Glanemann & Claudia Rubie
