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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 (0.1mg/kg/day), liraglutide s.c. (0.4mg/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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE190218 | GEO | 2022/01/14

REPOSITORIES: GEO

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Liraglutide + PYY3-36 combination therapy mimics effects of Roux-en-Y bypass on early NAFLD whilst lacking-behind in metabolic improvements.

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