title: Trehalose prevents adipocyte hypertrophy and mitigates insulin resistance in mice with established obesity.
abstract: Our group recently demonstrated that simultaneous administration of trehalose with a high-fat diet (HFD) suppresses adipocyte hypertrophy and mitigates insulin resistance in mice. For the present study, we hypothesized that similar effects of trehalose would be observed in mice with previously-established obesity. Obese mice were fed a HFD and drinking water containing 0.3 or 2.5% (weight/volume) trehalose or distilled water (DW) ad libitum for 8 wk. After 7 wk intake of a HFD and trehalose, fasting serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) in the 0.3% Tre/HFD group were significantly lower than those in the DW/HFD group (p<0.05). After 8 wk of treatment, mesenteric adipocytes in the 0.3% Tre/HFD group showed significantly less hypertrophy than those in the DW/HFD group. Mechanistic analysis indicated that levels of high molecular weight (HMW) adiponectin in the serum of the 0.3% Tre/HFD group were significantly higher than those in the DW/HFD group. The expression levels of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) messenger RNA (mRNA) in muscle were also significantly increased by trehalose intake. Our data therefore suggest that administration of trehalose to obese mice mitigates insulin resistance by suppressing adipocyte hypertrophy and increasing serum HMW adiponectin, resulting in upregulation of IRS-1, and IRS-2 expression in muscle. These results further suggest that trehalose is a functional saccharide that may be used to prevent the progression of insulin resistance.
authors.affiliation: R&D Center, Hayashibara Co. Ltd.
authors.forename: Chikako
authors.initials: C
authors.lastname: Arai
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyake
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Mizote
authors.forename: Chiyo
authors.initials: C
authors.lastname: Yoshizane
authors.forename: Yohko
authors.initials: Y
authors.lastname: Hanaya
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Koide
authors.forename: Mika
authors.initials: M
authors.lastname: Yamada
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Hanaya
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Arai
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fukuda
mesh_terms: D052242:Adiponectin / Q000819:agonists / Q000097:blood / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D005260:Female; D005786:Gene Expression Regulation; D006946:Hyperinsulinism / Q000178:diet therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D055504:Insulin Receptor Substrate Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology*; D024821:Metabolic Syndrome / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D011897:Random Allocation; D014199:Trehalose / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D014199:Trehalose