Fonseca Liza, Castillo Valeska, Aguirre Carolina, Silva Paulo, Ronco Ana M, Llanos Miguel
Laboratorio de Nutrición y Regulación Metabólica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
Departamento Ciencias de la Salud, Carrera de Nutrición y Dietética, Facultad de Medicina, Pontificia Universidad Católica de Chile, Campus San Joaquín, Santiago, Chile.
J Nutr Metab. 2019 Jan 17;2019:2806519. doi: 10.1155/2019/2806519. eCollection 2019.
Several reports have shown that stress during lactation causes long-term metabolic and hormonal disruptions. In this study, we designed experiments to evaluate the effects of stress during lactation on the abundance of Type 1 cannabinoid/endocannabinoid receptors (CB1R) in epididymal fat and liver and development of insulin resistance in adult mice. During the whole lactation, male mice pups were daily subcutaneously injected (days 1-21) with a saline solution to produce a soft nociceptive stress (NS). Mice body weight and food intake were periodically evaluated. Adult animals were subsequently subjected to an insulin tolerance test and some days later sacrificed to evaluate the amount of epididymal fat and abundance of CB1R and adipophilin in liver and epididymal adipose tissue. Lipoprotein lipase (LPL) activity and circulating levels of leptin, adiponectin, and corticosterone were also evaluated. In this model, NS during lactation significantly increased the amount of epididymal fat and induced insulin resistance in adult mice. In addition, a significantly increased abundance of CB1R and adipophilin in epididymal fat and liver was observed, together with elevated circulating levels of leptin and corticosterone. Adult NS animals also had low plasmatic adiponectin and, although nonsignificant, had a sustained trend to a greater LPL activity associated with epididymal fat. These results indicate that increased abundance of CB1R in liver and epididymal fat alters tissue functionality likely associated with development of systemic metabolic alterations such as insulin resistance in adult mice. All these pathophysiological facts are long-term consequences of nociceptive stress during lactation.
多项报告表明，哺乳期的应激会导致长期的代谢和激素紊乱。在本研究中，我们设计了实验来评估哺乳期应激对成年小鼠附睾脂肪和肝脏中1型大麻素/内源性大麻素受体（CB1R）丰度以及胰岛素抵抗发展的影响。在整个哺乳期，雄性幼鼠每天（第1 - 21天）皮下注射盐溶液以产生轻度伤害性应激（NS）。定期评估小鼠体重和食物摄入量。随后对成年动物进行胰岛素耐量试验，几天后处死以评估附睾脂肪量以及肝脏和附睾脂肪组织中CB1R和脂肪亲和素的丰度。还评估了脂蛋白脂肪酶（LPL）活性以及瘦素、脂联素和皮质酮的循环水平。在该模型中，哺乳期的NS显著增加了成年小鼠的附睾脂肪量并诱导了胰岛素抵抗。此外，观察到附睾脂肪和肝脏中CB1R和脂肪亲和素的丰度显著增加，同时瘦素和皮质酮的循环水平升高。成年NS动物的血浆脂联素水平也较低，并且尽管不显著，但附睾脂肪相关的LPL活性有持续升高的趋势。这些结果表明，肝脏和附睾脂肪中CB1R丰度的增加改变了组织功能，这可能与成年小鼠全身性代谢改变如胰岛素抵抗的发展有关。所有这些病理生理事实都是哺乳期伤害性应激的长期后果。
