title: Abnormalities in myo-inositol metabolism associated with type 2 diabetes in mice fed a high-fat diet: benefits of a dietary myo-inositol supplementation.
abstract: We previously reported that a chronic supplementation with myo-inositol (MI) improved insulin sensitivity and reduced fat accretion in mice. We then tested the potency of such dietary intervention in the prevention of insulin resistance in C57BL/6 male mouse fed a high-fat diet (HFD). In addition, some abnormalities in inositol metabolism were reported to be associated with insulin resistance in several animal and human studies. We then investigated the presence of such anomalies (i.e. inosituria and an inositol intra-tissue depletion) in this diet-induced obesity (DIO) mouse model, as well as the potential benefit of a MI supplementation for inositol intra-tissue deficiency correction. HFD (60 % energy from fat) feeding was associated with inosituria and inositol intra-tissue depletion in the liver and kidneys. MI supplementation (0·58 mg/g per d) restored inositol pools in kidneys (partially) and liver (fully). HFD feeding for 4 months induced ectopic lipid redistribution to liver and muscles, fasting hyperglycaemia and hyperinsulinaemia, insulin resistance and obesity that were not prevented by MI supplementation, despite a significant improvement in insulin sensitivity parameter K insulin tolerance test and a reduction in white adipose tissue (WAT) mass ( - 17 %, P< 0·05). MI supplementation significantly reduced fatty acid synthase activity in epididymal WAT, which might explain its beneficial, but modest, effect on WAT accretion in HFD-fed mice. Finally, we found some abnormalities in inositol metabolism in association with a diabetic phenotype (i.e. insulin resistance and fasting hyperglycaemia) in a DIO mouse model. Dietary MI supplementation was efficient in the prevention of inositol intra-tissue depletion, but did not prevent insulin resistance or obesity efficiently in this mouse model.
authors.affiliation: Lyon University,F-69600Oullins,France.
authors.forename: Marine L
authors.initials: ML
authors.lastname: Croze
authors.affiliation: CarMeN Laboratory, INSERM U1060, Bâtiment IMBL, INSA-Lyon,20 Avenue Albert Einstein,F-69621Villeurbanne Cedex,France.
authors.forename: Alain
authors.initials: A
authors.lastname: Géloën
authors.affiliation: Lyon University,F-69600Oullins,France.
authors.forename: Christophe O
authors.initials: CO
authors.lastname: Soulage
mesh_terms: D054392:Adipokines / Q000097:blood; D052436:Adipose Tissue, White / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D059305:Diet, High-Fat; D019587:Dietary Supplements; D064429:Fatty Acid Synthases / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007294:Inositol / Q000008:administration & dosage* / Q000032:analysis / Q000172:deficiency / Q000378:metabolism* / Q000652:urine; D007333:Insulin Resistance; D007668:Kidney / Q000737:chemistry; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control
chemical_list: D054392:Adipokines; D007294:Inositol; D064429:Fatty Acid Synthases
keywords:   myo-Inositol; Diabetes; High-fat diet; Inosituria; Insulin resistance; Obesity