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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Chen, J; Haase, N; Haange, SB; Sucher, R; Münzker, J; Jäger, E; Schischke, K; Seyfried, F; von, Bergen, M; Hankir, MK; Krügel, U; Fenske, WK.
Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk.
Mol Metab. 2021; 48:101214 Doi: 10.1016/j.molmet.2021.101214 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Co-Autor*innen der Med Uni Graz
Sucher Robert

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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 for morbid obesity, but mechanisms underlying sustained feeding suppression remain largely elusive. This study investigated whether Roux-en-Y gastric bypass (RYGB) interacts with obesity-associated hypothalamic inflammation to restore central leptin signaling as a mechanistic account for post-operative 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 signaling, microglia reactivity, and the inflammatory pathways were examined to be under the control of gut microbiota-derived circulating signaling. RESULTS: RYGB, other than CR-induced adiposity reduction, ameliorates hypothalamic gliosis, inflammatory signaling, and ER stress, which are linked to enhanced hypothalamic leptin signaling and responsiveness. Mechanistically, we demonstrate that RYGB interferes with hypothalamic ER stress and toll-like receptor 4 (TLR4) signaling 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 signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the post-surgical altered gut microbial environment.
Find related publications in this database (using NLM MeSH Indexing)
Animals - administration & dosage
Caloric Restriction - administration & dosage
Diet, High-Fat - adverse effects
Disease Models, Animal - administration & dosage
Gastric Bypass - methods
Gastrointestinal Microbiome - administration & dosage
Hypothalamus - metabolism
Inflammation - metabolism
Leptin - metabolism
Male - administration & dosage
Microglia - metabolism
Neurons - metabolism
Obesity, Morbid - etiology, surgery
Rats - administration & dosage
Rats, Wistar - administration & dosage
Signal Transduction - administration & dosage
Treatment Outcome - administration & dosage
Weight Loss - administration & dosage

Find related publications in this database (Keywords)
Roux-en-Y gastric Bypass
Bariatric surgery
Hypothalamic inflammation
Endoplasmic reticulum stress
Toll-like receptor 4
Gut microbiota-brain axis
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