Department of Physiology, Ribeirao Preto Medical School University of Sao Paulo , Sao Paulo , Brazil.
Am J Physiol Endocrinol Metab. 2018 Jul 1;315(1):E29-E37. doi: 10.1152/ajpendo.00358.2017. Epub 2018 Feb 13.
Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.
新生儿营养变化会对能量平衡产生持久影响。脂联素影响食物摄入和体重。本研究旨在探讨新生儿营养编程对脂联素中枢刺激的影响。雄性 Wistar 大鼠在产后第 3 天（小窝，SL）、10 天（正常窝，NL）或 16 天（大窝，LL）的窝中分为 3 只。我们评估了 60 天的体重增加、脂联素浓度和白色脂肪组织重量。我们检查了 SL、NL 和 LL 大鼠对体重增加、食物摄入、氧气消耗（V̇o）、呼吸交换率（RER）、热量测定、运动活动、下丘脑磷酸化 AMP 激活蛋白激酶（AMPK）表达和棕色脂肪组织中解偶联蛋白（UCP）-1 的反应在接受脂联素中枢刺激后。断奶后，尽管与 NL 大鼠的食物摄入量相似，SL 大鼠仍保持较高的体重增加。LL 大鼠在断奶时体重较低，但随后赶上并增加了食物摄入量。在 PN60 时，两组均降低了血浆脂联素浓度。SL 大鼠的白色脂肪组织增加。脂联素的中枢注射降低了 NL 大鼠的体重和食物摄入量，并增加了 V̇o、RER、热量测定、p-AMPK 和 UCP-1 的表达，但对 SL 和 LL 大鼠没有影响，与各自的载体组相比。总之，新生儿喂养不足和过度喂养会导致青少年和成年早期体重增加。对脂联素中枢作用的无反应导致新生儿营养编程引起的成年期能量平衡失衡。
