Joly Amélie, Thoumas Jean-Louis, Lambert Anne, Caillon Estelle, Leulier François, De Vadder Filipe
Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5242, UCBL Lyon-1, 69007, Lyon, France.
Nutr Metab (Lond). 2024 Dec 2;21(1):100. doi: 10.1186/s12986-024-00879-9.
Dysregulation of energy metabolism, including hyperglycemia, insulin resistance and fatty liver have been reported in a substantial proportion of lean children. However, non-obese murine models recapitulating these features are lacking to study the mechanisms underlying the development of metabolic dysregulations in lean children. Here, we develop a model of diet-induced metabolic dysfunction without obesity in juvenile mice by feeding male and female mice a diet reflecting Western nutritional intake combined with protein restriction (mWD) during 5 weeks after weaning. mWD-fed mice (35% fat, 8% protein) do not exhibit significant weight gain and have moderate increase in adiposity compared to control mice (16% fat, 20% protein). After 3 weeks of mWD, juvenile mice have impaired glucose metabolism including hyperglycemia, insulin resistance and glucose intolerance. mWD also triggers hepatic metabolism alterations, as shown by the development of simple liver steatosis. Both male and female mice fed with mWD displayed metabolic dysregulation, which a probiotic treatment with Lactiplantibacillus plantarum WJL failed to improve. Overall, mWD-fed mice appear to be a good preclinical model to study the development of diet-induced metabolic dysfunction without obesity in juveniles.
据报道，相当一部分瘦儿童存在能量代谢失调，包括高血糖、胰岛素抵抗和脂肪肝。然而，缺乏重现这些特征的非肥胖小鼠模型来研究瘦儿童代谢失调发展的潜在机制。在此，我们通过在断奶后5周给雄性和雌性小鼠喂食反映西方营养摄入并结合蛋白质限制的饮食（mWD），建立了一种幼年小鼠饮食诱导的无肥胖代谢功能障碍模型。与对照小鼠（16%脂肪，20%蛋白质）相比，喂食mWD的小鼠（35%脂肪，8%蛋白质）体重没有显著增加，肥胖程度有适度增加。mWD喂养3周后，幼年小鼠出现葡萄糖代谢受损，包括高血糖、胰岛素抵抗和葡萄糖不耐受。mWD还引发肝脏代谢改变，表现为单纯性肝脂肪变性。喂食mWD的雄性和雌性小鼠均表现出代谢失调，植物乳杆菌WJL的益生菌治疗未能改善这种情况。总体而言，喂食mWD的小鼠似乎是研究幼年饮食诱导的无肥胖代谢功能障碍发展的良好临床前模型。
