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1.
J Cell Biochem ; 118(1): 31-42, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27191548

RESUMEN

Dietary methionine restriction (MR) increases longevity and improves healthspan in rodent models. Young male C57BL/6J mice were placed on MR to assess effects on bone structure and formation. Mice were fed diets containing 0.86% or 0.12% methionine for 5 weeks. Fasting blood plasma was analyzed for metabolic and bone-related biomarkers. Tibiae were analyzed by histomorphometry, while femurs were analyzed by micro-CT and biomechanically using 4-point bending. MR mice had reduced plasma glucose and insulin, while FGF21 and FGF23 increased. Plasma levels of osteocalcin and osteoprotegrin were unaffected, but sclerostin and procollagen I decreased. MR induced bone marrow fat accretion, antithetical to the reduced fat depots seen throughout the body. Cortical bone showed significant decreases in Bone Tissue Density (BTD). In trabecular bone, mice had decreased BTD, bone surface, trabecula and bone volume, and trabecular thickness.. Biomechanical testing showed that on MR, bones were significantly less stiff and had reduced maximum load and total work, suggesting greater fragility. Reduced expression of RUNX2 occurred in bone marrow of MR mice. These results suggest that MR alters bone remodeling and apposition. In MR mice, miR-31 in plasma and liver, and miR-133a, miR-335-5p, and miR-204 in the bone marrow was elevated. These miRNAs were shown previously to target and regulate Osterix and RUNX2 in bone, which could inhibit osteoblast differentiation and function. Therefore, dietary MR in young animals alters bone structure by increasing miRNAs in bone and liver that can target RUNX2. J. Cell. Biochem. 118: 31-42, 2017. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Alimentos Formulados/efectos adversos , Regulación de la Expresión Génica , Metionina/deficiencia , MicroARNs/metabolismo , Tibia/metabolismo , Animales , Glucemia/metabolismo , Densidad Ósea , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Masculino , Ratones , Tibia/patología
2.
Sci Rep ; 5: 8886, 2015 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-25744495

RESUMEN

Dietary methionine restriction (MR) in rodents increased lifespan despite higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia, which are symptoms associated with increased risk for cardiovascular disease. We investigated this paradoxical effect of MR on cardiac function using young, old, and apolipoprotein E-deficient (ApoE-KO) mice. Indeed, MR animals exhibited higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia with a molecular pattern consistent with cardiac stress while maintaining the integrity of cardiac structure. Baseline cardiac function, which was measured by non-invasive electrocardiography (ECG), showed that young MR mice had prolonged QRS intervals compared with control-fed (CF) mice, whereas old and ApoE-KO mice showed similar results for both groups. Following ß-adrenergic challenge, responses of MR mice were either similar or attenuated compared with CF mice. Cardiac contractility, which was measured by isolated heart retrograde perfusion, was similar in both groups of old mice. Finally, the MR diet induced secretion of cardioprotective hormones, adiponectin and fibroblast growth factor 21 (FGF21), in MR mice with concomitant alterations in cardiac metabolic molecular signatures. Our findings demonstrate that MR diet does not alter cardiac function in mice despite the presence of hyperhomocysteinemia because of the adaptive responses of increased adiponectin and FGF21 levels.


Asunto(s)
Adaptación Fisiológica , Sistema Cardiovascular/fisiopatología , Dieta , Hiperhomocisteinemia/etiología , Hiperhomocisteinemia/fisiopatología , Metionina , Adiponectina/metabolismo , Agonistas Adrenérgicos beta/administración & dosificación , Agonistas Adrenérgicos beta/farmacología , Factores de Edad , Animales , Apolipoproteínas E/deficiencia , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Susceptibilidad a Enfermedades , Factores de Crecimiento de Fibroblastos/metabolismo , Masculino , Ratones , Ratones Noqueados , Transducción de Señal
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