title: Supplemental epilactose prevents metabolic disorders through uncoupling protein-1 induction in the skeletal muscle of mice fed high-fat diets.
abstract: Obesity is one of the major health problems throughout the world. The present study investigated the preventive effect of epilactose--a rare non-digestible disaccharide--on obesity and metabolic disorders in mice fed high-fat (HF) diets. Feeding with HF diets increased body weight gain, fat pad weight and adipocyte size in mice (P<0·01), and these increases were effectively prevented by the use of supplemental epilactose without influencing food intake (P<0·01). Caecal pools of SCFA such as acetic and propionic acids in mice fed epilactose were higher compared with mice not receiving epilactose. Supplemental epilactose increased the expression of uncoupling protein (UCP)-1, which enhances energy expenditure, to 2-fold in the gastrocnemius muscle (P=0·04) and to 1·3-fold in the brown adipose tissue (P=0·02) in mice fed HF diets. Feeding HF diets induced pro-inflammatory macrophage infiltration into white adipose tissue, as indicated by the increased expression of monocyte chemotactic protein-1, TNF-α and F4/80, and these increases were attenuated by supplemental epilactose. In differentiated myogenic-like C2C12 cells, propionic acid, but not acetic or n-butyric acids, directly enhanced UCP-1 expression by approximately 2-fold (P<0·01). Taken together, these findings indicate that the epilactose-mediated increase in UCP-1 in the skeletal muscle and brown adipose tissue can enhance whole-body energy expenditure, leading to effective prevention of obesity and metabolic disorders in mice fed HF diets. It is suggested that propionic acid--a bacterial metabolite--acts as a mediator to induce UCP-1 expression in skeletal muscles.
authors.affiliation: 1Department of Biofunctional Science and Technology,Graduate School of Biosphere Science,Hiroshima University,Higashi-Hiroshima 739-8528,Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: 2Department of Bioengineering Sciences,Graduate School of Bioagricultural Sciences,Nagoya University,Nagoya 464-8601,Japan.
authors.forename: Teruyo
authors.initials: T
authors.lastname: Ojima-Kato
authors.affiliation: 3Division of Applied Bioscience,Research Faculty of Agriculture,Hokkaido University,Sapporo 060-8589,Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Saburi
authors.affiliation: 3Division of Applied Bioscience,Research Faculty of Agriculture,Hokkaido University,Sapporo 060-8589,Japan.
authors.forename: Haruhide
authors.initials: H
authors.lastname: Mori
authors.affiliation: 3Division of Applied Bioscience,Research Faculty of Agriculture,Hokkaido University,Sapporo 060-8589,Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsui
authors.affiliation: 1Department of Biofunctional Science and Technology,Graduate School of Biosphere Science,Hiroshima University,Higashi-Hiroshima 739-8528,Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: 1Department of Biofunctional Science and Technology,Graduate School of Biosphere Science,Hiroshima University,Higashi-Hiroshima 739-8528,Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D002001:Adipose Tissue, Brown / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use; D019440:Anti-Obesity Agents / Q000378:metabolism / Q000627:therapeutic use*; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D004187:Disaccharides / Q000378:metabolism / Q000627:therapeutic use*; D004734:Energy Metabolism; D005285:Fermentation; D000069196:Gastrointestinal Microbiome; D007473:Ion Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation; D008297:Male; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism*; D009765:Obesity / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D056692:Prebiotics; D011422:Propionates / Q000378:metabolism; D011897:Random Allocation; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; D004187:Disaccharides; D007473:Ion Channels; D024101:Mitochondrial Proteins; D056692:Prebiotics; D011422:Propionates; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C047464:epilactose; C029658:propionic acid
keywords: C control; Epi epilactose; Epilactose; HF high fat; MCP-1 monocyte chemotactic protein; Obesity; Propionic acid; Skeletal muscle; Std standard diet; UCP-1 uncoupling protein-1; Uncoupling protein