High fat diet-induced maternal overweight predisposes higher body weight and altered hypothalamic feeding neural pathway in the offspring

Abstract:

Objective：To examine the influences of high fat diet-induced maternal overweight on the development of obesity in the offspring and the potential molecular mechanisms with focus on the changes of hypothalamic feeding circuitry. Methods：Female SD rats were allowed to either high fat（HF） diet or normal chow（NC） diet for 14 weeks，and then mated with healthy male rats. The off－spring born to HF or NC dams（designated as HF-O or NC-O） were assigned to normal chow diet. Birth weight and body weight of HF-O and NC-O were measured. Animals were sacrificed on postnatal day 40 and 160（P40 and P160）. The characteristics of orexi－genic NPY（Neuorpeptide Y） and anorexigenic POMC（Proopiomelanocortin） expression in the hypothalamaus were determined by im－munohistochemical staining. Results：Compared with NC-O，HF-O had higher birth weight（t=4.18，P=0.000），and higher body weight during childhood in male（t=3.46，P=0.009） and female（t=21.99，P=0.000）. But HF-O tended to have normal body weights in male（t=2.69，P=0.028） and female（t=2.49，P=0.037） during adult－hood although still higher than NC-O. HF-O also increased gonadal fat pad weight during childhood（t=3.03，P=0.007） and adulthood（t=2.40，P=0.027） compared with NC-O. Immunohis－tochemical staining showed the NPY levels were increased in the hypothalamic arcuate nucleus of HF-O compared with NC-O，but there was no significant change of POMC expression be－tween the groups，both during childhood and adulthood. Conclusion：High fat diet-induced maternal overweight predisposes obese development in the offspring，especially at the beginning of the birth and childhood stage，which may possibly be associated with the altered hypothalamic feeding neural pathways.