Enduring consequences of maternal obesity for brain inflammation and behavior of offspring.
Obesity is well characterized as a systemic inflammatory condition, and is also associated with cognitive disruption, suggesting a link between the two. We assessed whether peripheral inflammation in maternal obesity may be transferred to the offspring brain, in particular, the hippocampus, and thereby result in cognitive dysfunction. Rat dams were fed a high-saturated-fat diet (SFD), a high-trans-fat diet (TFD), or a low-fat diet (LFD) for 4 wk prior to mating, and remained on the diet throughout pregnancy and lactation. SFD/TFD exposure significantly increased body weight in both dams and pups compared to controls. Microglial activation markers were increased in the hippocampus of SFD/TFD pups at birth. At weaning and in adulthood, proinflammatory cytokine expression was strikingly increased in the periphery and hippocampus following a bacterial challenge [lipopolysaccharide (LPS)] in the SFD/TFD groups compared to controls. Microglial activation within the hippocampus was also increased basally in SFD rats, suggesting a chronic priming of the cells. Finally, there were marked changes in anxiety and spatial learning in SFD/TFD groups. These effects were all observed in adulthood, even after the pups were placed on standard chow at weaning, suggesting these outcomes were programmed early in life.
Bilbo
Staci D
SD
Duke University, Department of Psychology and Neuroscience, Durham, NC 27708, USA. staci.bilbo@duke.edu
Tsang
Verne
V
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000008:administration & dosage*; D004734:Energy Metabolism; D005260:Female; D020738:Leptin / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000503:physiopathology*; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014886:Weaning
D016207:Cytokines; D004041:Dietary Fats; D020738:Leptin