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
Affiliations
Anna Nakamura
Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Health Science Laboratory, Keio Research Institute at SFC, Fujisawa, Kanagawa 252-0882, Japan
Yoko Yokoyama
Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Health Science Laboratory, Keio Research Institute at SFC, Fujisawa, Kanagawa 252-0882, Japan
Kazuki Tanaka
Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Kanagawa 210-0821, Japan
Giorgia Benegiamo
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland
Akiyoshi Hirayama
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Qi Zhu
Health Science Laboratory, Keio Research Institute at SFC, Fujisawa, Kanagawa 252-0882, Japan; Department of Environment and Information Studies, Keio University, Fujisawa, Kanagawa 252-0882, Japan
Naho Kitamura
Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Health Science Laboratory, Keio Research Institute at SFC, Fujisawa, Kanagawa 252-0882, Japan
Taichi Sugizaki
Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Kohkichi Morimoto
Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Hiroshi Itoh
Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Shinji Fukuda
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Kanagawa 210-0821, Japan; Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Johan Auwerx
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland
Kazuo Tsubota
Health Science Laboratory, Keio Research Institute at SFC, Fujisawa, Kanagawa 252-0882, Japan; Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan; Corresponding author
Mitsuhiro Watanabe
Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Health Science Laboratory, Keio Research Institute at SFC, Fujisawa, Kanagawa 252-0882, Japan; Department of Environment and Information Studies, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan; Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan; Corresponding author
Summary: 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.
