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Physiology and Biochemistry

Effects of a novel polyphenol-rich plant extract on body composition, inflammation, insulin sensitivity, and glucose homeostasis in obese mice

International Journal of Obesity volume 45, pages 2016–2027 (2021)Cite this article

Subjects

Abstract

Background/objectives

The worldwide prevalence of obesity, metabolic syndrome and type 2 diabetes (T2D) is reaching epidemic proportions that urge the development of new management strategies. Totum-63 is a novel, plant-based polyphenol-rich active principle that has been shown to reduce body weight, fasting glycemia, glucose intolerance, and fatty liver index in obese subjects with prediabetes. Here, we investigated the effects and underlying mechanism(s) of Totum-63 on metabolic homeostasis in insulin-resistant obese mice.

Methods

Male C57Bl6/J mice were fed a high-fat diet for 12 weeks followed by supplementation with Totum-63 for 4 weeks. The effects on whole-body energy and metabolic homeostasis, as well as on tissue-specific inflammation and insulin sensitivity were assessed using a variety of immunometabolic phenotyping tools.

Results

Totum-63 decreased body weight and fat mass in obese mice, without affecting lean mass, food intake and locomotor activity, and increased fecal energy excretion and whole-body fatty acid oxidation. Totum-63 reduced fasting plasma glucose, insulin and leptin levels, and improved whole-body insulin sensitivity and peripheral glucose uptake. The expression of insulin receptor β and the insulin-induced phosphorylation of Akt/PKB were increased in liver, skeletal muscle, white adipose tissue (WAT) and brown adipose tissue (BAT). Hepatic steatosis was also decreased by Totum-63 and associated with a lower expression of genes involved in fatty acid uptake, de novo lipogenesis, inflammation, and fibrosis. Furthermore, a significant reduction in pro-inflammatory macrophages was also observed in epidydimal WAT. Finally, a potent decrease in BAT mass associated with enhanced tissue expression of thermogenic genes was found, suggesting BAT activation by Totum-63.

Conclusions

Our results show that Totum-63 reduces inflammation and improves insulin sensitivity and glucose homeostasis in obese mice through pleiotropic effects on various metabolic organs. Altogether, plant-derived Totum-63 might constitute a promising novel nutritional supplement for alleviating metabolic dysfunctions in obese people with or without T2D.

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Fig. 1: Totum-63 decreases body weight, fat mass and energy assimilation efficiency in HFD-fed mice.
Fig. 2: Totum-63 improves whole-body metabolic homeostasis in obese mice.
Fig. 3: Totum-63 improves systemic and tissue-specific insulin sensitivity in obese mice.
Fig. 4: Totum-63 reduces hepatic steatosis, inflammation and fibrosis in obese mice.
Fig. 5: Totum-63 reduces inflammation in white adipose tissues from obese mice.
Fig. 6: Totum-63 promotes thermogenic program and reduces inflammation in brown adipose tissue from obese mice.

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Author information

Authors and Affiliations

  1. Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands

    Hendrik J. P. van der Zande, Joost M. Lambooij, Anna Zawistowska-Deniziak, Frank Otto & Bruno Guigas

  2. Valbiotis R&D Riom Center, Riom, France

    Vivien Chavanelle, Yolanda Otero & Pascal Sirvent

  3. Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

    Louise Lantier & Owen P. McGuinness

  4. Vanderbilt Mouse Metabolic Phenotyping Center, Nashville, TN, USA

    Louise Lantier & Owen P. McGuinness

  5. Valbiotis R&D Perigny Center, Périgny, France

    Florian Le Joubioux & Sébastien L. Peltier

  6. Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands

    Martin Giera

  7. LIENSs UMR CNRS 7266, La Rochelle Université, La Rochelle, France

    Thierry Maugard

Authors
  1. Hendrik J. P. van der Zande
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Corresponding author

Correspondence to Bruno Guigas.

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Conflict of interest

VC, YO, FLJ, SLP, and PS are all employees of Valbiotis. SLP and PS are listed as co-inventors on Totum-63 patent and possess company stock. None of the other authors have any potential competing interests. This work was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grants DK059637 and S10RR028101 (LL, OMcG), the NWO project 184.034.019 (MG), and Valbiotis (BG). Study design, collection of the data, analysis and interpretation of the results, writing and decision to submit the article for publication was performed by Guigas’ group at the Leiden University Medical Center, in agreement with Valbiotis.

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van der Zande, H.J.P., Lambooij, J.M., Chavanelle, V. et al. Effects of a novel polyphenol-rich plant extract on body composition, inflammation, insulin sensitivity, and glucose homeostasis in obese mice. Int J Obes 45, 2016–2027 (2021). https://doi.org/10.1038/s41366-021-00870-x

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  • DOI: https://doi.org/10.1038/s41366-021-00870-x

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