RESUMO
Early-life adversity (ELA) is linked with the increased risk for inflammatory and metabolic diseases in later life, but the mechanisms remain poorly understood. Intestinal epithelial glucose transporters sodium-glucose-linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) are the major route for intestinal glucose uptake but have also received increased attention as modulators of inflammatory and metabolic diseases. Here, we tested the hypothesis that early weaning (EW) in pigs, an established model of ELA, alters the development of epithelial glucose transporters and coincides with elevated markers of metabolic inflammation. The jejunum and ileum of 90-day-old pigs previously exposed to EW (16 days wean age), exhibited reduced SGLT1 activity (by â¼ 30%, P < 0.05) than late weaned (LW, 28 days wean age) controls. In contrast, GLUT2-mediated glucose transport was increased (P = 0.003) in EW pigs than in LW pigs. Reciprocal changes in SGLT1- and GLUT2-mediated transport coincided with transporter protein expression in the intestinal brush-border membranes (BBMs) that were observed at 90 days and 150 days of age. Ileal SGLT1-mediated glucose transport and BBM expression were inhibited by the ß-adrenergic receptor (ßAR) blocker propranolol in EW and LW pigs. In contrast, propranolol enhanced ileal GLUT2-mediated glucose transport (P = 0.015) and brush-border membrane vesicle (BBMV) abundance (P = 0.035) in LW pigs, but not in EW pigs. Early-weaned pigs exhibited chronically elevated blood glucose and C-reactive protein (CRP) levels, and adipocyte hypertrophy and upregulated adipogenesis-related gene expression in visceral adipose tissue. Altered development of intestinal glucose transporters by EW could underlie the increased risk for later life inflammatory and metabolic diseases.NEW & NOTEWORTHY These studies reveal that early-life adversity in the form of early weaning in pigs causes a developmental shift in intestinal glucose transport from SGLT1 toward GLUT2-mediated transport. Early weaning also induced markers of metabolic inflammation including persistent elevations in blood glucose and the inflammatory marker CRP, along with increased visceral adiposity. Altered intestinal glucose transport might contribute to increased risk for inflammatory and metabolic diseases associated with early-life adversity.
Assuntos
Glicemia , Propranolol , Animais , Glicemia/metabolismo , Feminino , Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Transportador 1 de Glucose-Sódio/genética , Suínos , DesmameRESUMO
La mastitis en novillas es un problema que ha alcanzado importantes dimensiones a medida que las explotaciones lecheras se han especializado. Las hembras bovinas son susceptibles a infecciones intramamarias (IIM) desde el momento en que la glándula mamaria se ha desarrollado completamente en el feto. Factores relacionados al animal, al medio en que se desarrolla y al manejo incrementan o reducen el riesgo de contraer IIM. El grupo de bacterias mas usualmente asociadas con IIM en novillas gestantes son los Staphylococcus coagulasa negativos (SCN), pero otras bacterias como Staphylococus aureus, Mycoplasma spp, Streptococcus uberis y Streptococcus agalactiae, son tambien importantes agentes etiológicos de IIM. Las alternativas al manejo de la mastitis en novillas están dirigidas a la reducción de factores de riesgo y se complementan con la administración de terapias de sellamiento físico del pezón, desinfectantes o antibióticas, previa evaluación de los programas de sanidad de hato con que cuenta cada explotación.