title: Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice.
abstract: 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.
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Kanagawa, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishimaki
authors.forename: Ikuroh
authors.initials: I
authors.lastname: Ohsawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004734:Energy Metabolism; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D006003:Glycogen / Q000737:chemistry / Q000378:metabolism; D006859:Hydrogen / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000209:etiology / Q000517:prevention & control; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D014867:Water; D005346:Fibroblast Growth Factors; D006859:Hydrogen; D006003:Glycogen