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Molecular Hydrogen Improves Obesity and Diabetes by Inducing Hepatic FGF21 and Stimulating Energy Metabolism in db/db Mice
Author(s) -
Kamimura Naomi,
Nishimaki Kiyomi,
Ohsawa Ikuroh,
Ohta Shigeo
Publication year - 2011
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2011.6
Subject(s) - endocrinology , medicine , fgf21 , glycogen , steatosis , fatty liver , oxidative stress , leptin , chemistry , diabetes mellitus , type 2 diabetes , fatty acid , obesity , beta oxidation , triglyceride , metabolism , carbohydrate metabolism , leptin receptor , biology , receptor , fibroblast growth factor , biochemistry , disease , cholesterol
Recent extensive studies have revealed that molecular hydrogen (H 2 ) has great potential for improving oxidative stress‐related diseases by inhaling H 2 gas, injecting saline with dissolved H 2 , or drinking water with dissolved H 2 (H 2 ‐water); however, little is known about the dynamic movement of H 2 in a body. First, we show that hepatic glycogen accumulates H 2 after oral administration of H 2 ‐water, explaining why consumption of even a small amount of H 2 over a short span time efficiently improves various disease models. This finding was supported by an in vitro experiment in which glycogen solution maintained H 2 . Next, we examined the benefit of ad libitum drinking H 2 ‐water to type 2 diabetes using db/db obesity model mice lacking the functional leptin receptor. Drinking H 2 ‐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 H 2 ‐water significantly controlled fat and body weights, despite no increase in consumption of diet and water. Moreover, drinking H 2 ‐water decreased levels of plasma glucose, insulin, and triglyceride, the effect of which on hyperglycemia was similar to diet restriction. To examine how drinking H 2 ‐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, H 2 stimulated energy metabolism as measured by oxygen consumption. The present results suggest the potential benefit of H 2 in improving obesity, diabetes, and metabolic syndrome.