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Sibutramine high-doses effects in cafeteria diet-induced obese rats
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  • Published: 11 February 2026

Sibutramine high-doses effects in cafeteria diet-induced obese rats

  • Filipe M. Ribeiro1,2 na1,
  • Henny K. Lima1 na1,
  • Camila F. A. Ribeiro3,
  • Osmar N. Silva4,
  • Guilherme Mendonça3,
  • Nathalia Cavichiolli de Oliveira3,
  • Rinaldo W. Pereira1,
  • Alinne P. de Castro3 &
  • …
  • Octávio L. Franco1,3 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Dysbiosis
  • Experimental models of disease
  • Liver
  • Obesity

Abstract

Obesity, defined as excessive fat accumulation that impairs health, is a global challenge with high mortality rates. Sibutramine, a centrally acting anorectic, was widely used in obesity treatment due to its effects on appetite control and weight loss. It represented a key step in anti-obesity pharmacotherapy before being withdrawn in many countries. This study evaluates how a high sibutramine dose (10 mg.kg.day−1 followed by 13 mg.kg.day−1) influences body weight, biochemical profiles, liver and intestinal health, and gut microbiota composition in rats subjected to a cafeteria diet for 16 weeks. Rats treated with sibutramine exhibited a 10.93% reduction in body weight and improved glycemic control compared to untreated groups. Sibutramine modulated lipid profiles by lowering total cholesterol and increasing HDL levels in controlled diet groups. The treatment attenuated liver damage markers (AST and ALT) and increased intestinal crypt depth, suggesting gut integrity. The elevated sibutramine dose led to distinct microbiota shifts, partially reversing cafeteria diet-induced dysbiosis by increasing SCFA-producing genera, including Bacillus, Marvinbryantia, and Bifidobacterium. However, dietary factors remained the dominant driver of microbial composition. These findings underscore the impact of sibutramine’s dosing on gut microbiota and reinforce its role in obesity-related health improvements.

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Data availability

The gut microbiota sequencing dataset is available under BioProject ID PRJNA1139136. The data can be accessed via the following link: https://www.ncbi.nlm.nih.gov/sra/PRJNA1139227.

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Acknowledgements

This study was supported by Coordenação de Aperfeiçoamento de Pessoal e Nı́vel Superior (CAPES), Fundação de Apoio ao Desenvolvimento de Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT), Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (FINEP) and Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF).

Author information

Author notes

  1. Filipe M. Ribeiro and Henny K. Lima have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Center for Proteomics and Biochemical Analysis, Postgraduate Program in Genomic Sciences and Biotechnology, Catholic University of Brasília, Brasília, Brazil

    Filipe M. Ribeiro, Henny K. Lima, Rinaldo W. Pereira & Octávio L. Franco

  2. Laboratory of Molecular Exercise Physiology, University Center, UDF, Brasília, Brazil

    Filipe M. Ribeiro

  3. Postgraduate Program in Biotechnology, S-Inova Biotech, Dom Bosco Catholic University, Campo Grande, Brazil

    Camila F. A. Ribeiro, Guilherme Mendonça, Nathalia Cavichiolli de Oliveira, Alinne P. de Castro & Octávio L. Franco

  4. UniEvangélica, Evangelical University of Goiás, Anápolis, GO, 75083- 515, Brazil

    Osmar N. Silva

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Contributions

H.K.L., O.L.F. conceived the study and designed experiments.; F.M.R., H.K.L., C.F.A.R., and O.L.F. developed methodology and analyzed the data; H.K.L. and C.F.A.R. performed the experiments work; O.N.S. performed histological assessment.; G.M., N.C., R.W.P., and A.P.C. helped with data analysis.; F.M.R., O.L.F. wrote the manuscript.

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Correspondence to Octávio L. Franco.

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Ribeiro, F.M., Lima, H.K., Ribeiro, C.F.A. et al. Sibutramine high-doses effects in cafeteria diet-induced obese rats. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35214-0

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  • Received: 14 March 2025

  • Accepted: 03 January 2026

  • Published: 11 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-35214-0

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Keywords

  • Gut microbiota
  • Sibutramine
  • Obesity
  • Cafeteria diet
  • Liver health
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