title: A genistein-enriched diet neither improves skeletal muscle oxidative capacity nor prevents the transition towards advanced insulin resistance in ZDF rats.
abstract: Genistein, a natural food compound mainly present in soybeans, is considered a potent antioxidant and to improve glucose homeostasis. However, its mechanism of action remains poorly understood. Here, we analyzed whether genistein could antagonize the progression of the hyperinsulinemic normoglycemic state (pre-diabetes) toward full-blown T2DM in Zucker Diabetic Fatty (ZDF) rats by decreasing mitochondrial oxidative stress and improving skeletal muscle oxidative capacity. Rats were assigned to three groups: (1) lean control (CNTL), (2) fa/fa CNTL, and (3) fa/fa genistein (GEN). GEN animals were subjected to a 0.02% (w/w) genistein-enriched diet for 8 weeks, whereas CNTL rats received a standard diet. We show that genistein did not affect the overall response to a glucose challenge in ZDF rats. In fact, genistein may exacerbate glucose intolerance as fasting glucose levels were significantly higher in fa/fa GEN (17.6 ± 0.7 mM) compared with fa/fa CNTL animals (14.9 ± 1.4 mM). Oxidative stress, established by electron spin resonance (ESR) spectroscopy, carbonylated protein content and UCP3 levels, remained unchanged upon dietary genistein supplementation. Furthermore, respirometry measurements revealed no effects of genistein on mitochondrial function. In conclusion, dietary genistein supplementation did not improve glucose homeostasis, alleviate oxidative stress, or augment skeletal muscle metabolism in ZDF rats.
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Bianca W J
authors.initials: BW
authors.lastname: van Bree
authors.affiliation: Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Lenaers
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: Nabben
authors.affiliation: Department of Toxicogenomics, GROW School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jacco J
authors.initials: JJ
authors.lastname: Briedé
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.|Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Jörgensen
authors.affiliation: Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: Hoeks
authors.affiliation: Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D004032:Diet; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D007333:Insulin Resistance; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D048789:Phytoestrogens; D019833:Genistein; D005947:Glucose