Carvalho Adriana Lelis, DeMambro Victoria E, Guntur Anyonya R, Le Phuong, Nagano Kenichi, Baron Roland, de Paula Francisco José Albuquerque, Motyl Katherine J
Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine.
Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
J Cell Physiol. 2018 Feb;233(2):1585-1600. doi: 10.1002/jcp.26062. Epub 2017 Aug 4.
There is a growing and alarming prevalence of obesity and the metabolic syndrome in type I diabetic patients (T1DM), particularly in adolescence. In general, low bone mass, higher fracture risk, and increased marrow adipose tissue (MAT) are features of diabetic osteopathy in insulin-deficient subjects. On the other hand, type 2 diabetes (T2DM) is associated with normal or high bone mass, a greater risk of peripheral fractures, and no change in MAT. Therefore, we sought to determine the effect of weight gain on bone turnover in insulin-deficient mice. We evaluated the impact of a 6-week high-fat (HFD) rich in medium chain fatty acids or low-fat diet (LFD) on bone mass and MAT in a streptozotocin (STZ)-induced model using male C57BL/6J mice at 8 weeks of age. Dietary intervention was initiated after diabetes confirmation. At the endpoint, lower non-fasting glucose levels were observed in diabetic mice fed with high fat diet compared to diabetic mice fed the low fat diet (STZ-LFD). Compared to euglycemic controls, the STZ-LFD had marked polydipsia and polyphagia, as well as reduced lean mass, fat mass, and bone parameters. Interestingly, STZ-HFD mice had higher bone mass, namely less cortical bone loss and more trabecular bone than STZ-LFD. Thus, we found that a HFD, rich in medium chain fatty acids, protects against bone loss in a T1DM mouse model. Whether this may also translate to T1DM patients who are overweight or obese in respect to maintenance of bone mass remains to be determined through longitudinal studies.
1型糖尿病患者(T1DM)中肥胖和代谢综合征的患病率正在上升,且令人担忧,尤其是在青少年中。一般来说,骨量低、骨折风险高以及骨髓脂肪组织(MAT)增加是胰岛素缺乏受试者糖尿病性骨病的特征。另一方面,2型糖尿病(T2DM)与骨量正常或偏高、外周骨折风险增加以及MAT无变化有关。因此,我们试图确定体重增加对胰岛素缺乏小鼠骨转换的影响。我们在8周龄的雄性C57BL/6J小鼠的链脲佐菌素(STZ)诱导模型中,评估了富含中链脂肪酸的6周高脂饮食(HFD)或低脂饮食(LFD)对骨量和MAT的影响。在确认糖尿病后开始饮食干预。在实验终点,与喂食低脂饮食的糖尿病小鼠(STZ-LFD)相比,喂食高脂饮食的糖尿病小鼠的非空腹血糖水平更低。与血糖正常的对照组相比,STZ-LFD组有明显的多饮、多食,以及瘦体重、脂肪量和骨参数降低。有趣的是,STZ-HFD小鼠的骨量更高,即皮质骨丢失更少,小梁骨比STZ-LFD组更多。因此,我们发现富含中链脂肪酸的高脂饮食可预防T1DM小鼠模型中的骨质流失。这是否也适用于超重或肥胖的T1DM患者以维持骨量,仍有待通过纵向研究来确定。