Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

Anna Nakamura; Yoko Yokoyama; Kazuki Tanaka; Giorgia Benegiamo; Akiyoshi Hirayama; Qi Zhu; Naho Kitamura; Taichi Sugizaki; Kohkichi Morimoto; Hiroshi Itoh; Shinji Fukuda; Johan Auwerx; Kazuo Tsubota; Mitsuhiro Watanabe

doi:10.1016/j.isci.2020.101522

Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

iScience. 2020 Sep 2;23(9):101522. doi: 10.1016/j.isci.2020.101522. eCollection 2020 Sep 25.

Authors

Anna Nakamura^{1

2}, Yoko Yokoyama^{1

2}, Kazuki Tanaka^{1

3

4}, Giorgia Benegiamo⁵, Akiyoshi Hirayama³, Qi Zhu^{2

6}, Naho Kitamura^{1

2}, Taichi Sugizaki⁷, Kohkichi Morimoto⁷, Hiroshi Itoh⁷, Shinji Fukuda^{3

4

8}, Johan Auwerx⁵, Kazuo Tsubota^{2

9}, Mitsuhiro Watanabe^{1

2

6

7

9}

Affiliations

¹ Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan.
² Health Science Laboratory, Keio Research Institute at SFC, Fujisawa, Kanagawa 252-0882, Japan.
³ Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
⁴ Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Kanagawa 210-0821, Japan.
⁵ Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
⁶ Department of Environment and Information Studies, Keio University, Fujisawa, Kanagawa 252-0882, Japan.
⁷ Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
⁸ Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
⁹ Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.

Abstract

Asperuloside (ASP) is an iridoid glycoside that is extracted from Eucommia leaves. Eucommia is used in traditional Chinese medicine and has a long history of benefits on health and longevity. Here, we investigated the impact of ASP on obesity-related metabolic disorders and show that ASP reduces body weight gain, glucose intolerance, and insulin resistance effectively in mice fed with a high-fat diet (HFD). Intestinal dysbiosis is closely linked with metabolic disorders. Our data indicate that ASP achieves these benefits on metabolic homeostasis by reversing HFD-induced gut dysbiosis and by changing gut-derived secondary metabolites and metabolic signaling. Our results indicate that ASP may be used to regulate gut microbiota for the treatment of obesity and type 2 diabetes.

Keywords: Human Metabolism; Microbiome.