Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Diabetes Obes Metab. 2019 Apr;21(4):866-875. doi: 10.1111/dom.13591. Epub 2018 Dec 21.
To examine whether the glucagon-like peptide-1 receptor agonist liraglutide could be used in juvenile male and female rats as an anti-obesity/diabetic pharmaceutical to prevent not only adolescent obesity/hyperglycaemia, but also early-adult onset obesity.
Pregnant dams were fed either standard chow or a high-fat, high-sucrose diet (HFSD) from gestational day 2, throughout pregnancy and lactation. Offspring were weaned onto the respective maternal diet. Juveniles received daily subcutaneous injection of liraglutide (50 μg/kg, from postnatal day [PND]30 to PND40 and 200 μg/kg from PND40 to PND60) or vehicle. Food intake, body weight and glycaemic levels were evaluated across the experimental period.
Chronic liraglutide administration in juveniles prevented body weight gain in males and retained a normoglycaemic profile in both male and female rats.
These preclinical data suggest that maternal and early-life consumption of an HFSD increases caloric intake, body weight gain and hyperglycaemia, a collective set of unwanted metabolic effects that appear to be treatable in juveniles with liraglutide pharmacotherapy intervention.
研究胰高血糖素样肽-1 受体激动剂利拉鲁肽是否可用于雄性和雌性未成年大鼠，作为一种预防青少年肥胖/高血糖的抗肥胖/糖尿病药物，不仅能预防青少年肥胖/高血糖，还能预防成年早期肥胖。
从妊娠第 2 天开始，妊娠和哺乳期的孕鼠给予标准饲料或高脂肪、高蔗糖饮食（HFSD）。幼鼠断奶后给予相应的母代饮食。从出生后第 30 天（PND30）到 PND40 天，幼鼠每天接受皮下注射利拉鲁肽（50μg/kg），从 PND40 天到 PND60 天接受 200μg/kg 利拉鲁肽或载体注射。在整个实验期间评估食物摄入量、体重和血糖水平。
在幼鼠中进行的利拉鲁肽慢性给药可预防雄性大鼠体重增加，并维持雄性和雌性大鼠的正常血糖水平。
这些临床前数据表明，母体和生命早期的 HFSD 摄入会增加热量摄入、体重增加和高血糖，这些不良的代谢影响似乎可以通过利拉鲁肽药物治疗干预来治疗。
