Mounting evidence suggests that an overactive immune response during pregnancy may alter the development of the central nervous system in the foetus. An increased concentration of pro-inflammatory cytokines has been demonstrated in amniotic fluid of obese pregnancy. This study investigate if low-chronic inflammation, during brain development may have enduring effects on hypothalamic immune response leading to autonomic disturbances and sympathetic mediated hypertension arising from maternal obesity.Design and method:
C57BL/6J female mice were fed either a standard chow (7% simple sugars,3% fat) or a highly palatable obesogenic diet (33% simple sugars, 16% fat) 6 weeks prior to mating and throughout gestation and lactation. Offspring were then weaned onto standard chow. Serum samples were collected at gestational day 18 (GD 18), postnatal day 21 and 3 months of age for multiplex cytokine assay. At 3 months of age, blood pressure and pressor response to acute restraint stress were recorded by radiotelemetry. Renal norephinephrine was measured by ELISA. Hypothalamic Interleukin-6 (IL-6) mRNA expression was monitored in juvenile (pre-hypertensive) offspring using QPCR.Results:
Diet-induced obese dams demonstrated an enhanced serum pro-inflammatory cytokine profile at GD 18. Serum IL-6 and necrosis factor alpha (TNF- α) concentrations were twice as high in offspring of obese dams (OffOb) as neonates (P < 0.05, n = 6) and adult (P < 0.05, n = 10). Heightened hypothalamic IL-6 mRNA expression was obtained in juvenile OffOb compared with OffCon mice. At 3 months of age, OffOb mice demonstrated sympathetic mediated hypertension with a heightened pressure response to stress and renal norephineprine concentration.Conclusions:
Low-chronic inflammation in obese pregnancy have enduring effects on hypothalamic immune populations in the offspring leading to autonomic disturbances and an early onset sympathetic mediated hypertension.