Chen Hui, Morris Margaret J
Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Obesity (Silver Spring). 2009 Jul;17(7):1356-62. doi: 10.1038/oby.2009.56. Epub 2009 Mar 12.
Maternal obesity due to long-term high-fat diet (HFD) consumption leads to faster growth in offspring during suckling, and increased adiposity at 20 days of age. Decreased expression of the orexigenic neuropeptide Y (NPY) and increased anorexigenic proopiomelanocortin (POMC) mRNA expression were observed in the fed state. However, hunger is the major drive to eat and hypothalamic appetite regulators change in response to meals. Therefore, it is important to compare both satiated and fasting states. Female Sprague-Dawley rats (8 weeks old) were fed a cafeteria-style HFD (15.33 kJ/g) or chow for 5 weeks before mating, with the same diet continuing throughout gestation and lactation. At postnatal day 20, male pups were killed either after overnight fasting or in the fed state. Pups from obese dams were hyperphagic during both pre- and postweaning periods. Pups from obese dams had higher hypothalamic mRNA expression of POMC and NPY Y1 receptor, but lower hypothalamic melanocortin-4 receptor (MC4R) and its downstream target single-minded gene 1 (Sim1), in the fed state. Overnight fasting reduced circulating glucose, insulin, and leptin and increased hypothalamic NPY Y1 receptor mRNA in pups from both lean and obese dams. Hypothalamic NPY and agouti-related protein (AgRP) were only increased by fasting in pups from obese dams; reductions in MC4R and Sim1 were only seen in pups from lean dams. At weaning, the suppressed orexigenic signals in offspring from obese dams were normalized after overnight fasting, although anorexigenic signaling appeared impaired in these animals. This may contribute to their hyperphagia and faster growth.
长期食用高脂饮食（HFD）导致的母体肥胖会使后代在哺乳期间生长加快，并在20日龄时肥胖增加。在进食状态下，观察到促食欲神经肽Y（NPY）表达降低，而厌食性阿黑皮素原（POMC）mRNA表达增加。然而，饥饿是进食的主要驱动力，下丘脑食欲调节因子会因进食而发生变化。因此，比较饱腹和禁食状态很重要。雌性Sprague-Dawley大鼠（8周龄）在交配前喂食自助式HFD（15.33 kJ/g）或普通饲料5周，在整个妊娠和哺乳期持续相同饮食。在出生后第20天，雄性幼崽在禁食过夜后或进食状态下被处死。肥胖母鼠的幼崽在断奶前后均食欲亢进。肥胖母鼠的幼崽在进食状态下下丘脑POMC和NPY Y1受体的mRNA表达较高，但下丘脑黑皮质素-4受体（MC4R）及其下游靶点单 minded基因1（Sim1）较低。禁食过夜会降低瘦母鼠和肥胖母鼠幼崽的循环葡萄糖、胰岛素和瘦素水平，并增加下丘脑NPY Y1受体mRNA。下丘脑NPY和刺鼠相关蛋白（AgRP）仅在肥胖母鼠的幼崽禁食后增加；MC4R和Sim1的降低仅在瘦母鼠的幼崽中出现。断奶时，肥胖母鼠后代中被抑制的促食欲信号在禁食过夜后恢复正常，尽管这些动物的厌食信号似乎受损。这可能导致它们食欲亢进和生长加快。
