Molecular Hydrogen Improves Obesity and Diabetes by Inducing Hepatic FGF21 and Stimulating Energy Metabolism in db/db Mice

Authors

  • Naomi Kamimura,

    1. Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Kanagawa, Japan
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  • Kiyomi Nishimaki,

    1. Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Kanagawa, Japan
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  • Ikuroh Ohsawa,

    1. Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Kanagawa, Japan
    2. Department of Environmental Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
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  • Shigeo Ohta

    Corresponding author
    1. Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Kanagawa, Japan
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(ohta@nms.ac.jp)

Abstract

Recent extensive studies have revealed that molecular hydrogen (H2) has great potential for improving oxidative stress-related diseases by inhaling H2 gas, injecting saline with dissolved H2, or drinking water with dissolved H2 (H2-water); however, little is known about the dynamic movement of H2 in a body. First, we show that hepatic glycogen accumulates H2 after oral administration of H2-water, explaining why consumption of even a small amount of H2 over a short span time efficiently improves various disease models. This finding was supported by an in vitro experiment in which glycogen solution maintained H2. Next, we examined the benefit of ad libitum drinking H2-water to type 2 diabetes using db/db obesity model mice lacking the functional leptin receptor. Drinking H2-water reduced hepatic oxidative stress, and significantly alleviated fatty liver in db/db mice as well as high fat-diet-induced fatty liver in wild-type mice. Long-term drinking H2-water significantly controlled fat and body weights, despite no increase in consumption of diet and water. Moreover, drinking H2-water decreased levels of plasma glucose, insulin, and triglyceride, the effect of which on hyperglycemia was similar to diet restriction. To examine how drinking H2-water improves obesity and metabolic parameters at the molecular level, we examined gene-expression profiles, and found enhanced expression of a hepatic hormone, fibroblast growth factor 21 (FGF21), which functions to enhance fatty acid and glucose expenditure. Indeed, H2 stimulated energy metabolism as measured by oxygen consumption. The present results suggest the potential benefit of H2 in improving obesity, diabetes, and metabolic syndrome.

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