Priestman D A, van der Spoel A C, Butters T D, Dwek R A, Platt F M
Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK.
Diabetes Obes Metab. 2008 Feb;10(2):159-66. doi: 10.1111/j.1463-1326.2006.00701.x.
To determine the mechanism of weight loss caused by high doses of N-butyldeoxynojirimycin (NB-DNJ) in healthy lean and leptin-deficient obese (ob/ob) mice.
Healthy lean and obese mice were treated with NB-DNJ by the following methods: admixed with their diet, delivered by subcutaneously implanted mini-pumps or by intraperitoneal or intracerebroventricular (ICV) injection. Daily changes in body weight and food intake were recorded during the experimental period. The effect of NB-DNJ treatment on subcutaneous adipose tissue and on epididymal fat pads was measured.
Lean mice treated with NB-DNJ, admixed with their diet, lost weight in the form of adipose tissue. This resulted in a 40% reduction in skin thickness (control, 358 +/- 11 microm; NB-DNJ treated 203 +/- 6 microm) and a reduction in epididymal fat pad weights after 5 weeks of treatment at 2400 mg/kg/day (control, 0.0154 +/- 0.001; NB-DNJ treated, 0.0026 +/- 0.0005 as ratios of fat pad weight to total body weight). Following the depletion of adipose tissue mass, the mice grew normally and did not have any reduction in lean mass. Obese mice treated with NB-DNJ also lost weight or gained weight at a greatly reduced rate compared with non-treated controls. Body weights at 6 months of age were: lean control, 29.10 +/- 1.15 g; lean NB-DNJ treated, 22.73 +/- 0.29 g; obese control, 63.25 +/- 1.5 g; obese NB-DNJ treated from 5 weeks of age, 35.30 +/- 1.68 g; obese NB-DNJ treated from 12 weeks of age, 38.84 +/- 1.26 g. Both the lean and obese groups of mice treated with NB-DNJ ate up to 30% less than untreated controls. Daily food intake (powder diet) were: lean control, 4.15 +/- 0.54 g; obese control, 4.14 +/- 0.2 g; lean NB-DNJ treated 2.9 +/- 0.37 g; obese NB-DNJ treated, 2.88 +/- 0.47 g. Mice treated with the N-substituted galactose imino sugar analogue, N-butyldeoxygalactonojirimycin (NB-DGJ) did not lose weight. Mice experienced similar weight loss or lack of weight gain when fed a restricted diet that mimics the drug-induced level of food consumption. Delivery of 2 nmol NB-DNJ by ICV injection into lean mice also caused similar reductions in food intake. Food intake: saline vehicle, 4.30 +/- 0.12 g; NB-DNJ, 3.37 +/- 0.19 g; NB-DGJ, 4.03 +/- 0.16 g; 2-deoxyglucose, 4.7 +/- 0.15 g.
NB-DNJ causes weight loss as a result of reduced food consumption due to central appetite suppression.
确定高剂量N-丁基脱氧野尻霉素（NB-DNJ）导致健康瘦小鼠和瘦素缺乏型肥胖（ob/ob）小鼠体重减轻的机制。
通过以下方法用NB-DNJ处理健康瘦小鼠和肥胖小鼠：与它们的饮食混合、通过皮下植入微型泵给药或通过腹腔内或脑室内（ICV）注射。在实验期间记录体重和食物摄入量的每日变化。测量NB-DNJ处理对皮下脂肪组织和附睾脂肪垫的影响。
与饮食混合给予NB-DNJ处理的瘦小鼠以脂肪组织的形式减轻体重。这导致皮肤厚度减少40%（对照组，358±11微米；NB-DNJ处理组，203±6微米），并且在以2400毫克/千克/天的剂量处理5周后附睾脂肪垫重量减少（对照组，0.0154±0.001；NB-DNJ处理组，0.0026±0.0005，为脂肪垫重量与总体重的比值）。脂肪组织质量耗尽后，小鼠正常生长，瘦体重没有任何减少。与未处理的对照组相比，用NB-DNJ处理的肥胖小鼠也减轻了体重或以大大降低的速率增加体重。6个月龄时的体重分别为：瘦对照组，29.10±1.15克；瘦NB-DNJ处理组，22.73±0.29克；肥胖对照组，63.25±1.5克；5周龄开始用NB-DNJ处理的肥胖组，35.30±1.68克；12周龄开始用NB-DNJ处理的肥胖组，38.84±1.26克。用NB-DNJ处理的瘦小鼠和肥胖小鼠组的进食量均比未处理的对照组少30%。每日食物摄入量（粉状饮食）分别为：瘦对照组，4.15±0.54克；肥胖对照组，4.14±0.2克；瘦NB-DNJ处理组，2.9±0.37克；肥胖NB-DNJ处理组，2.88±0.47克。用N-取代的半乳糖亚氨基糖类似物N-丁基脱氧半乳糖野尻霉素（NB-DGJ）处理的小鼠没有减轻体重。当给小鼠喂食模拟药物诱导的食物消耗量水平限制饮食时，小鼠经历了类似的体重减轻或体重增加不足。通过ICV向瘦小鼠注射2纳摩尔NB-DNJ也导致食物摄入量有类似减少。食物摄入量：生理盐水载体组，4.30±0.12克；NB-DNJ组，3.37±0.19克；NB-DGJ组，4.03±0.16克；2-脱氧葡萄糖组，4.7±0.15克。
NB-DNJ由于中枢性食欲抑制导致食物消耗量减少，从而引起体重减轻。
Zotero 插件