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Article

Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats

1
Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Wurzburg, 97080 Wurzburg, Germany
2
Core Unit Systems Medicine, University of Wurzburg, 97080 Wurzburg, Germany
3
Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Wurzburg, 97080 Wurzburg, Germany
4
Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, University of Wurzburg, 97080 Wurzburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Susanna Iossa
Nutrients 2022, 14(1), 116; https://doi.org/10.3390/nu14010116
Received: 6 December 2021 / Revised: 23 December 2021 / Accepted: 24 December 2021 / Published: 28 December 2021
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. View Full-Text
Keywords: obesity; Roux-en-Y gastric bypass surgery; liraglutide; PYY3-36; hypothalamic gene expression obesity; Roux-en-Y gastric bypass surgery; liraglutide; PYY3-36; hypothalamic gene expression
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MDPI and ACS Style

Dischinger, U.; Heckel, T.; Bischler, T.; Hasinger, J.; Königsrainer, M.; Schmitt-Böhrer, A.; Otto, C.; Fassnacht, M.; Seyfried, F.; Hankir, M.K. Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats. Nutrients 2022, 14, 116. https://doi.org/10.3390/nu14010116

AMA Style

Dischinger U, Heckel T, Bischler T, Hasinger J, Königsrainer M, Schmitt-Böhrer A, Otto C, Fassnacht M, Seyfried F, Hankir MK. Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats. Nutrients. 2022; 14(1):116. https://doi.org/10.3390/nu14010116

Chicago/Turabian Style

Dischinger, Ulrich, Tobias Heckel, Thorsten Bischler, Julia Hasinger, Malina Königsrainer, Angelika Schmitt-Böhrer, Christoph Otto, Martin Fassnacht, Florian Seyfried, and Mohammed Khair Hankir. 2022. "Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats" Nutrients 14, no. 1: 116. https://doi.org/10.3390/nu14010116

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