Inulin increases the beneficial effects of rhubarb supplementation on high-fat high-sugar diet-induced metabolic disorders in mice: impact on energy expenditure, brown adipose tissue activity, and microbiota

ABSTRACT

Consumption of prebiotics and plant-based compounds have many beneficial health effects through modulation of gut microbiota composition and are considered as promising nutritional strategy for the treatment of metabolic diseases. In the present study, we assessed the separated and combined effects of inulin and rhubarb on diet-induced metabolic disease in mice. We showed that supplementation with both inulin and rhubarb abolished the total body and fat mass gain upon high-fat and high-sucrose diet (HFHS) as well as several obesity-associated metabolic disorders. These effects were associated with increased energy expenditure, lower whitening of the brown adipose tissue, higher mitochondria activity and increased expression of lipolytic markers in white adipose tissue. Despite modifications of intestinal gut microbiota and bile acid compositions by inulin or rhubarb alone, combination of both inulin and rhubarb had minor additional impact on these parameters. However, the combination of inulin and rhubarb increased the expression of several antimicrobial peptides and higher goblet cell numbers, thereby suggesting a reinforcement of the gut barrier. Together, these results suggest that the combination of inulin and rhubarb in mice potentiates beneficial effects of separated rhubarb and inulin on HFHS-related metabolic disease and could be considered as nutritional strategy for the prevention and treatment of obesity and related pathologies.

KEYWORDS:

• obesity
• high-fat diet high-sucrose
• obesity
• prebiotics
• brown adipose tissue
• energy expenditure
• inulin
• rhubarb extract
• gut microbiota

Availability of data and materials

All data generated or analyzed during this study are included in this published article and its supplementary information files. The raw amplicon sequencing data analyzed in this study will be accessible in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number https://www.ebi.ac.uk/ena/browser/view/PRJEB56494.

Authors’ contributions

MR, MVH, and PDC conceived and designed the study. MR performed the experiments and data analysis. MR, MVH, AdW, FS, and MVH contributed to samples collection, experiments, and data analysis. MR, MVH, and PDC performed the interpretation. MR prepared the samples for the sequencing. AP, MR, and GGM performed the analysis of bile acids and short chain fatty acids. GGM, NMD, AE, and PDC contributed to financial resources. MR, MVH, and PDC wrote the first version of the paper. All authors critically revised the manuscript and approved the final version before submission.

Acknowledgments

We thank A. Puel, H. Danthinne, B. Es Saadi, L. Gesche, R. M. Goebbels (at UCLouvain, Université catholique de Louvain) for their excellent technical support and assistance. We thank the members of WAGRALIM team and Nutrimicrobiota consortium for their fruitful discussions. C. Bouzin from the IREC imagery platform (2IP) from the Institut de Recherche Expérimentale et Clinique (IREC) for their excellent help.

Disclosure statement

PDC and AE are inventors on patent applications dealing with the use of gut microbiota and health. PDC was co-founder of Enterosys and The Akkermansia Company. The other authors declare no conflict of interest.

Authors’ information

^a Metabolism and Nutrition Research Group (MNUT), Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium, ^b WEL Research Institute (WELRI), Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), avenue Pasteur, 6, 1300 Wavre, Belgium, ^c Bioanalysis and Pharmacology of Bioactive Lipids Research Group (BPBL), Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Av. E. Mounier, 72 B1.72.01, 1200 Brussels Brussels, Belgium, ^d current address: Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden

Twitter

Matthias Van hul @matthias_vanhul, Francesco Suriano @suriano_f and Nathalie Delzenne @ndelzenne

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2178796

Additional information

Funding

PDC is research director at FRS-FNRS (Fonds de la Recherche Scientifique) and recipients of grants from FNRS (Projet de Recherche PDR-convention: FNRS T.0030.21-P, FRFS-WELBIO: WELBIO-CR-2019C-02R, WELBIO-CR-2022A-02 and EOS: program no. 30770923 and no. 40007505). AE is research associate from the FRS-FNRS and recipient of grants from FNRS (FRFS-WELBIO: WELBIO-CR-2019S-03, WELBIO-CR-2019S-03R, FNRS: J.0075.22). This work was supported by the SPW Walloon Region DG06 under the grant “ DGO6 NUTRIMICROBIOTA C-7906 PLMARSH” Wagralim; Fonds De La Recherche Scientifique - FNRS; Service Public de Wallonie.