title: Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats.
abstract: We previously found that thiamine mitigates metabolic disorders in spontaneously hypertensive rats, harboring defects in glucose and fatty acid metabolism. Mutation of thiamine transporter gene SLC19A2 is linked to type 2 diabetes mellitus. The current study extends our hypothesis that thiamine intervention may impact metabolic abnormalities in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, exhibiting obesity and metabolic disorders similar to human metabolic syndrome. Male OLETF rats (4 wk old) were given free access to water containing either 0.2% or 0% of thiamine for 21 and 51 wk. At the end of treatment, blood parameters and cardiac functions were analyzed. After sacrifice, organs weights, histological findings, and hepatic pyruvate dehydrogenase (PDH) activity in the liver were evaluated. Thiamine intervention averted obesity and prevented metabolic disorders in OLETF rats which accompanied mitigation of reduced lipid oxidation and increased hepatic PDH activity. Histological evaluation revealed that thiamine alleviated adipocyte hypertrophy, steatosis in the liver, heart, and skeletal muscle, sinusoidal fibrosis with formation of basement membranes (called pseudocapillarization) which accompanied significantly reduced expression of laminin β1 and nidogen-1 mRNA, interstitial fibrosis in the heart and kidney, fatty degeneration in the pancreas, thickening of the basement membrane of the vasculature, and glomerulopathy and mononuclear cell infiltration in the kidney. Cardiac and renal functions were preserved in thiamine treatment. Thiamine has a potential to prevent obesity and metabolic disorders in OLETF rats.
authors.affiliation: Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Kono
authors.forename: Fumio
authors.initials: F
authors.lastname: Terasaki
authors.forename: Kota
authors.initials: K
authors.lastname: Yasui
authors.forename: Akiko
authors.initials: A
authors.lastname: Soyama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Otsuka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fujita
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamane
authors.forename: Miki
authors.initials: M
authors.lastname: Manabe
authors.forename: Kazuya
authors.initials: K
authors.lastname: Usui
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kohda
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008659:Metabolic Diseases / Q000517:prevention & control*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010088:Oxidoreductases / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D012313:RNA / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D013831:Thiamine / Q000494:pharmacology / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007797:Laminin; D008562:Membrane Glycoproteins; C029967:nidogen; D014803:Vitamin B Complex; D012313:RNA; D010088:Oxidoreductases; D013831:Thiamine