Early life high-fat diet exposure maintains glucose tolerance and insulin sensitivity with a fatty liver and small brain size in the adult offspring

Abstract

Diet during pregnancy has long lasting consequences on the offspring, warranting a study on the impact of early exposure to a high fat diet on the adult offspring. We hypothesized that a prenatal n-6 enriched diet will have adverse metabolic outcomes on the adult offspring that may be reversed with a postnatal n-3 enriched diet. To test this hypothesis, we examined the adult offspring from three groups: (1) n-6 group: during gestation and lactation, dams consumed an n-6 polyunsaturated fatty acid enriched diet, (2) n-3 group: gestational n-6 diet was followed by an n-3 enriched diet during lactation, and (3) a control (CD) group that received standard diet throughout gestation and lactation. Offspring from all groups weaned to a control diet ad libitum. Beginning at postnatal day 2 (P < .03) and persisting at 360 days in males (P < .04), an increase in hypothalamic AgRP expression occurred in the n-6 and n-3 groups, with an increase in food intake (P = .01), and the n-3 group displaying lower body (P < .03) and brain (P < .05) weights. At 360 days, the n-6 and n-3 groups remained glucose tolerant and insulin sensitive, with increased phosphorylated-AMP-activated protein kinase (P < .05). n-6 group developed hepatic steatosis with reduced hepatic reflected as higher plasma microRNA-122 (P < .04) that targets pAMPK. We conclude that early life exposure to n-6 and n-3 led to hypothalamic AgRP-related higher food intake, with n-6 culminating in a fatty liver partially mitigated by postnatal n-3. While both diets preserved glucose tolerance and insulin sensitivity, postnatal n-3 displayed detrimental effects on the brain.