RESUMEN
Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.
Asunto(s)
Resistencia a la Insulina , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Proteínas del Tejido Nervioso , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismo , FenotipoRESUMEN
PURPOSE: The overexposure to synthetic glucocorticoids (GC) during pregnancy can predispose to metabolic diseases during adulthood. Vitamin D is not only crucial for fetal development, but also exerts direct effects on the GC sensitivity and down-regulates GC receptors. Given the vitamin D effects on glucocorticoid-related parameters, we aimed to investigate a possible protective role of maternal vitamin D administration on the glucose homeostasis of rats exposed to dexamethasone in utero. METHODS: Pregnant rats received dexamethasone (0.1 mg/kg, Dex) daily between the 14th and 19th days of pregnancy. A subgroup of dexamethasone-treated dams received oral administration of vitamin D (500UI, DexVD) during the whole gestation. The corresponding control groups of dams were included (CTL and VD groups, respectively). Male and female offspring were evaluated at 3, 6 and 12 months of age. RESULTS: Prenatal exposure to dexamethasone caused metabolic disruption in an age and sex-dependent manner being the older male offspring more susceptible to insulin resistance, fatty liver and beta-cell mass expansion than females. Furthermore, we demonstrated that prenatal GC led to glucose intolerance in male and female offspring in an age-dependent manner. Maternal vitamin D administration did not influence glucose intolerance but attenuated the insulin resistance, liver lipid accumulation and prevented the beta-cell mass expansion caused by prenatal dexamethasone in the male offspring. CONCLUSION: Maternal vitamin D administration mitigates metabolic disturbances that occur later in life in male rats exposed to GC in utero. Moreover, our data suggest vitamin D as an important nutritional supplement for pregnant overexposed to GC during gestation.
Asunto(s)
Dexametasona/efectos adversos , Glucocorticoides/efectos adversos , Enfermedades Metabólicas/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico , Animales , Femenino , Células Secretoras de Insulina/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Intercambio Materno-Fetal , Enfermedades Metabólicas/sangre , Enfermedades Metabólicas/inducido químicamente , Enfermedades Metabólicas/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas Wistar , Caracteres Sexuales , Triglicéridos/sangre , Triglicéridos/metabolismo , Vitamina D/farmacología , Vitaminas/farmacologíaRESUMEN
The aim of this study was to investigate the insulin clearance in diet-induced obese (DIO) mice submitted to acute endurance exercise (3h of treadmill exercise at 60-70% VO2max). Glucose-stimulated insulin secretion in isolated islets; ipGTT; ipITT; ipPTT; in vivo insulin clearance; protein expression in liver, skeletal muscle, and adipose tissue (insulin degrading enzyme (IDE), insulin receptor subunitß(IRß), phospho-Akt (p-Akt) and phospho-AMPK (p-AMPK)), and the activity of IDE in the liver and skeletal muscle were accessed. In DIO mice, acute exercise reduced fasting glycemia and insulinemia, improved glucose and insulin tolerance, reduced hepatic glucose production, and increased p-Akt protein levels in liver and skeletal muscle and p-AMPK protein levels in skeletal muscle. In addition, insulin secretion was reduced, whereas insulin clearance and the expression of IDE and IRß were increased in liver and skeletal muscle. Finally, IDE activity was increased only in skeletal muscle. In conclusion, we propose that the increased insulin clearance and IDE expression and activity, primarily, in skeletal muscle, constitute an additional mechanism, whereby physical exercise reduces insulinemia in DIO mice.