Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats
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. Metho...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/14/1/116 |
| _version_ | 1797497996016877568 |
|---|---|
| author | Ulrich Dischinger Tobias Heckel Thorsten Bischler Julia Hasinger Malina Königsrainer Angelika Schmitt-Böhrer Christoph Otto Martin Fassnacht Florian Seyfried Mohammed Khair Hankir |
| author_facet | Ulrich Dischinger Tobias Heckel Thorsten Bischler Julia Hasinger Malina Königsrainer Angelika Schmitt-Böhrer Christoph Otto Martin Fassnacht Florian Seyfried Mohammed Khair Hankir |
| author_sort | Ulrich Dischinger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:28:07Z |
| format | Article |
| id | doaj.art-91d473e136b643ffa07524c0dd054583 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T03:28:07Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-91d473e136b643ffa07524c0dd0545832023-11-23T12:04:26ZengMDPI AGNutrients2072-66432021-12-0114111610.3390/nu14010116Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese RatsUlrich Dischinger0Tobias Heckel1Thorsten Bischler2Julia Hasinger3Malina Königsrainer4Angelika Schmitt-Böhrer5Christoph Otto6Martin Fassnacht7Florian Seyfried8Mohammed Khair Hankir9Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyCore Unit Systems Medicine, University of Wurzburg, 97080 Wurzburg, GermanyCore Unit Systems Medicine, University of Wurzburg, 97080 Wurzburg, GermanyDepartment of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyDepartment of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyDepartment of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyDepartment of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyDepartment of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyDepartment of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyDepartment of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Wurzburg, 97080 Wurzburg, GermanyBackground: 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.https://www.mdpi.com/2072-6643/14/1/116obesityRoux-en-Y gastric bypass surgeryliraglutidePYY3-36hypothalamic gene expression |
| spellingShingle | Ulrich Dischinger Tobias Heckel Thorsten Bischler Julia Hasinger Malina Königsrainer Angelika Schmitt-Böhrer Christoph Otto Martin Fassnacht Florian Seyfried Mohammed Khair Hankir Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats Nutrients obesity Roux-en-Y gastric bypass surgery liraglutide PYY3-36 hypothalamic gene expression |
| title | Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats |
| title_full | Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats |
| title_fullStr | Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats |
| title_full_unstemmed | Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats |
| title_short | Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats |
| title_sort | roux en y gastric bypass and caloric restriction but not gut hormone based treatments profoundly impact the hypothalamic transcriptome in obese rats |
| topic | obesity Roux-en-Y gastric bypass surgery liraglutide PYY3-36 hypothalamic gene expression |
| url | https://www.mdpi.com/2072-6643/14/1/116 |
| work_keys_str_mv | AT ulrichdischinger rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT tobiasheckel rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT thorstenbischler rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT juliahasinger rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT malinakonigsrainer rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT angelikaschmittbohrer rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT christophotto rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT martinfassnacht rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT florianseyfried rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats AT mohammedkhairhankir rouxenygastricbypassandcaloricrestrictionbutnotguthormonebasedtreatmentsprofoundlyimpactthehypothalamictranscriptomeinobeserats |