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Titel (primär) Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk
Autor Chen, J.; Haase, N.; Haange, S.-B.; Sucher, R.; Münzker, J.; Jäger, E.; Schischke, K.; Seyfried, F.; von Bergen, M.; Hankir, M.K.; Krügel, U.; Fenske, W.K.;
Journal / Serie Molecular Metabolism
Erscheinungsjahr 2021
Department MOLSYB;
Band/Volume 48
Sprache englisch;
Supplements https://ars.els-cdn.com/content/image/1-s2.0-S2212877821000545-mmc1.docx
Keywords Roux-en-Y gastric bypass; Bariatric surgery; hypothalamic inflammation; endoplasmatic reticulum stress; toll-like receptor 4; gut microbiota-brain axis
Abstract

Objective

Hypothalamic inflammation and endoplasmic reticulum (ER) stress are extensively linked to leptin resistance and overnutrition-related diseases. Surgical intervention remains the most efficient long-term weight loss strategy in morbid obesity, but mechanisms underlying sustained feeding suppression remain largely elusive. This study investigates whether Roux-en-Y gastric bypass (RYGB) interacts with obesity-associated hypothalamic inflammation to restore central leptin signalling as a mechanistic account for postoperative appetite suppression.

Methods

RYGB or sham surgery was performed in high-fat diet-induced obese Wistar rats. Sham-operated rats were fed ad libitum or by weight matching to RYGB via calorie restriction (CR), before hypothalamic leptin signalling, microglia reactivity and inflammatory pathways were examined to be under the control of gut microbiota-derived circulating signalling.

Results

RYGB-, other than CR-induced adiposity reduction, ameliorates hypothalamic gliosis, inflammatory signalling and ER stress, which is linked to enhanced hypothalamic leptin signalling and responsiveness. Mechanistically, we demonstrate that RYGB interferes with hypothalamic ER stress and toll-like receptor 4 (TLR4) signalling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the altered gut microbial environment upon RYGB surgery.

Conclusions

Our data demonstrate that RYGB interferes with hypothalamic TLR4 signalling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the post-surgery altered gut microbial environment.

ID 24439
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=24439
Chen, J., Haase, N., Haange, S.-B., Sucher, R., Münzker, J., Jäger, E., Schischke, K., Seyfried, F., von Bergen, M., Hankir, M.K., Krügel, U., Fenske, W.K. (2021):
Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk
Mol. Metab. 48 , art. 101214