高脂饮食所致母代超重对子代体质量和下丘脑摄食神经通路的影响

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

摘要:

目的：以高脂饮食诱导的雌性大鼠为模型，探讨母代超重对子代体质量和下丘脑摄食神经通路的影响及其机制。方法：雌性SD大鼠，高脂饲料喂养14周，建立母代超重模型，与健康成年雄鼠交配，子代于出生第21天断奶后给予正常饲料喂养，分别在动物幼年期（40 d）和成年期（160 d）处死动物。测定并比较2组子代出生、幼年期、成年期体质量及体器官质量。免疫组织化学染色观察下丘脑弓状核部位促进食欲的神经肽Y（neuorpeptide Y，NPY）和抑制食欲的阿片促黑色素原（proopiome－lanocortin，POMC）表达。结果：超重母鼠子代有较高的出生体质量（t=4.18，P=0.000），且动物幼年期雄性（t=3.46，P=0.009）和雌性（t=21.99，P=0.000）体质量均明显高于对照组子代，动物成年期雄性（t=2.69，P=0.028）和雌性（t=2.49，P=0.037）体质量虽仍高于对照组子代，但有向正常发展的趋势。高脂组子代体内性腺周围脂肪含量在幼年期（t=3.03，P=0.007）和成年期（t=2.40，P=0.027）均较对照组子代增多。免疫组织化学结果显示高脂组子代在幼年期及成年期下丘脑弓状核部位NPY表达均增多，POMC表达在两组间未见明显差异。结论：高脂饮食诱导的母代超重可加重子代出生初期和幼年期肥胖的发生风险，但随着时间的推移，子代动物的体质量逐渐趋于正常，其作用机制可能与影响子代下丘脑摄食神经通路的正常调控有关。

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.