Sullivan Elinor L, Rivera Heidi M, True Cadence A, Franco Juliana G, Baquero Karalee, Dean Tyler A, Valleau Jeanette C, Takahashi Diana L, Frazee Tim, Hanna Genevieve, Kirigiti Melissa A, Bauman Leigh A, Grove Kevin L, Kievit Paul
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon.
Department of Biology, University of Portland, Portland, Oregon; and.
Am J Physiol Regul Integr Comp Physiol. 2017 Aug 1;313(2):R169-R179. doi: 10.1152/ajpregu.00309.2016. Epub 2017 Apr 12.
Maternal high-fat-diet (HFD) consumption during pregnancy decreased fetal body weight and impacted development of hypothalamic melanocortin neural circuitry in nonhuman primate offspring. We investigated whether these impairments during gestation persisted in juvenile offspring and examined the interaction between maternal and early postnatal HFD consumption. Adult dams consumed either a control diet (CTR; 15% calories from fat) or a high-saturated-fat diet (HFD; 37% calories from fat) during pregnancy. Offspring were weaned onto a CTR or HFD at ~8 mo of age. Offspring from HFD-fed dams displayed early catch-up growth and elevated body weight at 6 and 13 mo of age. Maternal and postnatal HFD exposure reduced the amount of agouti-related peptide fibers in the paraventricular nucleus of the hypothalamus. Postnatal HFD consumption also decreased the amount of agouti-related peptide fibers in the arcuate nucleus of the hypothalamus. Postnatal HFD was associated with decreased food intake and increased activity. These results support and extend our previous findings of maternal diet effects on fetal development and reveal, for the first time in a nonhuman primate model, that maternal HFD-induced disturbances in offspring body weight regulation extended past gestation into the juvenile period. Maternal HFD consumption increases the risk for offspring developing obesity, with the developmental timing of HFD exposure differentially impacting the melanocortin system and energy balance regulation. The present findings provide translational insight into human clinical populations, suggesting that profound health consequences may await individuals later in life following intrauterine and postnatal HFD exposure.
孕期母体食用高脂饮食（HFD）会降低胎儿体重，并影响非人灵长类后代下丘脑黑皮质素神经回路的发育。我们研究了这些孕期损伤在幼年后代中是否持续存在，并考察了母体和出生后早期食用HFD之间的相互作用。成年母猴在孕期食用对照饮食（CTR；15%的热量来自脂肪）或高饱和脂肪饮食（HFD；37%的热量来自脂肪）。后代在约8月龄时断奶，改为食用CTR或HFD。来自食用HFD母猴的后代在6月龄和13月龄时表现出早期追赶生长和体重增加。母体和出生后HFD暴露减少了下丘脑室旁核中刺鼠相关肽纤维的数量。出生后食用HFD也减少了下丘脑弓状核中刺鼠相关肽纤维的数量。出生后食用HFD与食物摄入量减少和活动增加有关。这些结果支持并扩展了我们之前关于母体饮食对胎儿发育影响的发现，并首次在非人灵长类动物模型中揭示，母体HFD诱导的后代体重调节紊乱从孕期持续到了幼年期。母体食用HFD会增加后代患肥胖症的风险，HFD暴露的发育时间对黑皮质素系统和能量平衡调节有不同影响。目前的研究结果为人类临床群体提供了转化性见解，表明子宫内和出生后HFD暴露可能会给个体晚年带来严重的健康后果。
