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

Abstract

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.

• Authors: Ulrich Dischinger, Tobias Heckel, Thorsten Bischler, Julia Hasinger, Malina Königsrainer, Angelika Schmitt-Böhrer, Christoph Otto, Martin Fassnacht, Florian Seyfried, Mohammed Khair Hankir
• Journal: Nutrients (Nutrients) Vol. 14 Issue 1 (Dec 28 2021) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 35010991 (Publication Type: Journal Article)

Chemical References

• Gastrointestinal Hormones
• Peptide Fragments
• Peptide YY
• peptide YY (3-36)
• Liraglutide

Topics

• Animals
• Body Weight
• Caloric Restriction
• Disease Models, Animal
• Energy Metabolism
• Gastric Bypass
• Gastrointestinal Hormones (pharmacology)
• Gene Expression (drug effects)
• Hypothalamus (metabolism)
• Liraglutide (pharmacology)
• Male
• Obesity
• Peptide Fragments (pharmacology)
• Peptide YY (pharmacology)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Transcriptome (drug effects)