Long Nathan M, Rule Daniel C, Tuersunjiang Nuermaimaiti, Nathanielsz Peter W, Ford Stephen P
Center for the Study of Fetal Programming, University of Wyoming, Laramie, Wyoming, United States of America; Department of Animal and Veterinary Sciences, Clemson University, Clemson, South Carolina, United States of America.
Department of Animal Science, University of Wyoming, Laramie, Wyoming, United States of America.
PLoS One. 2015 Apr 15;10(4):e0122152. doi: 10.1371/journal.pone.0122152. eCollection 2015.
Maternal obesity in women is increasing worldwide. The objective of this study was to evaluate differences in adipose tissue metabolism and function in adult male offspring from obese and control fed mothers subjected to an ad libitum feeding challenge. We developed a model in which obese ewes were fed 150% of feed provided for controls from 60 days before mating to term. All ewes were fed to requirements during lactation. After weaning, F1 male offspring were fed only to maintenance requirements until adulthood (control = 7, obese = 6), when they were fed ad libitum for 12 weeks with intake monitored. At the end of the feeding challenge offspring were given an intravenous glucose tolerance test (IVGTT), necropsied, and adipose tissue collected. During the feeding trial F1obese males consumed more (P < 0.01), gained more weight (P < 0.01) and became heavier (P < 0.05) than F1control males. During IVGTT, Obese F1 offspring were hyperglycemic and hypoinsulinemic (P < 0.01) compared to F1 control F1. At necropsy perirenal and omental adipose depots weights were 47% and 58% greater respectively and subcutaneous fat thickness 41% greater in F1obese vs. F1control males (P < 0.05). Adipocyte diameters were greater (P ≤ 0.04) in perirenal, omental and subcutaneous adipose depots in F1obese males (11, 8 and 7% increase vs. control, respectively). When adipose tissue was incubated for 2 hrs with C-14 labeled acetate, subcutaneous, perirenal, and omental adipose tissue of F1 obese males exhibited greater incorporation (290, 83, and 90% increase vs. control, respectively P < 0.05) of acetate into lipids. Expression of fatty acid transporting, binding, and syntheses mRNA and protein was increased (P < 0.05) compared to F1 control offspring. Maternal obesity increased appetite and adiposity associated with increased adipocyte diameters and increased fatty acid synthesis in over-nourished adult male offspring.
全球范围内,女性孕期肥胖的情况日益增多。本研究的目的是评估在随意进食挑战下,肥胖母亲和对照喂养母亲所生成年雄性后代脂肪组织代谢和功能的差异。我们建立了一个模型,即从配种前60天到足月,给肥胖母羊喂食的量是对照母羊的150%。所有母羊在哺乳期均按需求喂养。断奶后,F1代雄性后代仅按维持需求喂养直至成年(对照组 = 7只,肥胖组 = 6只),成年后随意进食12周并监测摄入量。在进食挑战结束时,对后代进行静脉葡萄糖耐量试验(IVGTT),然后进行剖检,并收集脂肪组织。在喂养试验期间,F1代肥胖雄性比F1代对照雄性消耗更多(P < 0.01)、体重增加更多(P < 0.01)且变得更重(P < 0.05)。在IVGTT期间,与F1代对照后代相比,肥胖的F1代后代血糖过高且胰岛素过低(P < 0.01)。剖检时,F1代肥胖雄性的肾周和网膜脂肪库重量分别比F1代对照雄性大47%和58%,皮下脂肪厚度大41%(P < 0.05)。F1代肥胖雄性的肾周、网膜和皮下脂肪库中的脂肪细胞直径更大(P ≤ 0.04)(分别比对照组增加11%、8%和7%)。当脂肪组织与C - 14标记的乙酸一起孵育2小时时,F1代肥胖雄性的皮下、肾周和网膜脂肪组织将乙酸掺入脂质的能力更强(分别比对照组增加290%、83%和90%,P < 0.05)。与F1代对照后代相比,脂肪酸转运、结合和合成相关mRNA及蛋白质的表达增加(P < 0.05)。孕期肥胖会增加营养过剩的成年雄性后代的食欲和肥胖程度,同时伴有脂肪细胞直径增大和脂肪酸合成增加。