Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA120871 | ENA |
REPOSITORIES: ENA
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Project description:Thiamine prevents diabetic complications, and its deficiency, resulting from mutation of thiamine transporter gene SLC19A2 has been linked to diabetes mellitus. We previously found that thiamine mitigates metabolic disorders in spontaneous hypertensive rats, harboring defects in glucose and fatty acid metabolism. The current study extends our hypothesis that that thiamine intervention may impact metabolic abnormalities in polyphagia-induced Otsuka Long-Evans Tokushima Fatty (OLETF) rats that lack functional cholecystokinin A receptors. Male OLETF rats exhibit progressive obesity and metabolic disorders similar to human metabolic syndrome. Male OLETF rats (4-week-old) were given free access to water containing either 0.2 % or 0 % of thiamine for 51 weeks. At the end of treatment, blood parameters and cardiac functions were analyzed. After sacrifice, the organs were removed and weights of organs and histological findings were evaluated. In addition, differential gene expression in the liver was analyzed. Thiamine intervention averted obesity, mainly resulting from reduction of visceral adiposity, and prevented metabolic disorders in OLETF rats. Histological evaluation revealed that thiamine alleviated adipocyte hypertrophy, steatosis in the liver, heart, and skeletal muscle, interstitial fibrosis in the heart and kidney, fatty degeneration in the pancreas, thickening of the basement membrane of vasculature, and glomerulopathy and mononuclear cell infiltration in the kidney. Cardiac and renal functions were preserved in thiamine treatment. Seventy-six genes showed at least two-fold difference in hepatic expression with thiamine treatment. Several of them participated in carbohydrate metabolism (Hk1, Pygb, Slc2a8, Rtn4, Rhbdl1, and Tspan8), lipid metabolism (Pla2g15, Por, and Lmf1), vascular physiology (S1pr1, Epha8, Rtn4, Slc7a13, Cdh15, Itga9, Cd151, Cd40lg, Nid1 and Lamb1), and carcinogenesis (Lmo7, Fgfr3, and Dmbt1). Modification of transcript expression well accorded with the findings of blood parameters and organ morphologies. Thiamine prevented polyphagia-induced obesity and metabolic and functional disorders in OLETF rats.
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