Department of Physiological Sciences, Institute of Biological Sciences, Federal University of Alfenas-MG, Alfenas, Brazil.
Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Brazil.
J Nutr Biochem. 2020 Dec;86:108494. doi: 10.1016/j.jnutbio.2020.108494. Epub 2020 Sep 11.
Overfeeding and rapid weight gain during early life are risk factors for the development of obesity in adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Cholecystokinin (CCK) acts on the central nervous system by elevating thermogenesis and the activity of anorectic neurons, modulating overall energy balance. Therefore, we tested the hypothesis that postnatal overfeeding impaired CCK effects. Pups were raised in either a litter of three (neonatal overnutrition/small litter group) or 12 (controls/normal litter group) pups per dam to study the effects of postnatal overfeeding on the central and peripheral CCK systems in adulthood. Rats raised in small litters became overweight during lactation and remained overweight as adults, with increased adiposity and plasma levels of lipids, glucose, insulin, and leptin. Neonatally over-nourished rats showed attenuation of gastric emptying and anorexigenic response to CCK, suggesting that offspring from the SL group may present CCK resistance as adult male rats. Consistent with this idea, overweight rats displayed impaired central response in c-Fos immunoreactivity on the nucleus tractus solitarius, area postrema, paraventricular nucleus, central amygdala, arcuate nucleus, and dorsomedial hypothalamus in response to peripheral CCK at adulthood. The small litter group of adult male rats also exhibited reduced norepinephrine- and CCK-stimulated thermogenesis. Unresponsiveness to the effects of CCK may contribute to overweight and metabolic dysfunctions observed in postnatally over-nourished adult rats. Thus, the involvement of an impaired CCK system, among other neurohormonal failures, may contribute to the development of obesity.
生命早期过度喂养和体重快速增加是成年后肥胖发展的危险因素。这种代谢失调可能是由发育关键期的内分泌失调引起的。胆囊收缩素（CCK）通过提高产热和厌食神经元的活性来作用于中枢神经系统，调节整体能量平衡。因此，我们测试了这样一个假设，即产后过度喂养会损害 CCK 的作用。通过将每只母鼠的幼崽数量分别设置为 3 只（新生期过度营养/小窝组）或 12 只（对照组/正常窝组）来研究产后过度喂养对成年期中枢和外周 CCK 系统的影响。在哺乳期，小窝组的大鼠体重增加，成年后仍超重，表现出脂肪增多和血浆中脂质、葡萄糖、胰岛素和瘦素水平升高。新生期过度营养的大鼠表现出胃排空和 CCK 抑制食欲反应的减弱，这表明 SL 组的后代可能在成年雄性大鼠中表现出 CCK 抵抗。与这一观点一致的是，超重大鼠在接受外周 CCK 刺激时，其孤束核、后极区、室旁核、中央杏仁核、弓状核和下丘脑背内侧核的 c-Fos 免疫反应中的中枢反应受损。成年雄性小窝组大鼠也表现出去甲肾上腺素和 CCK 刺激产热减少。对 CCK 作用的无反应可能是导致产后过度喂养的成年大鼠超重和代谢功能障碍的原因之一。因此，受损的 CCK 系统的参与，以及其他神经激素的失败，可能导致肥胖的发生。
