Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet
Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet
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DOI：
10.1152/ajpendo.00332.2001
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发表时间：
2002-04-01
影响因子：
5.1
通讯作者：
Thorens, B
中科院分区：
文献类型：
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作者：
Burcelin, M;Crivelli, V;Thorens, B
C57BL/6J小鼠以9个月喂食高脂，无碳水化合物饮食（HFD）。大约50％的小鼠变得肥胖和糖尿病（OBD），类似于10％瘦肉和糖尿病（LD），类似于10％瘦和非糖尿病（LND），并且与30％的中间表型相似。所有HFD小鼠均具有胰岛素耐药性。在禁食状态下，与正常的小鼠相比，在OBD小鼠中，OBD小鼠的全身葡萄糖清除率降低，在LD小鼠中不变，LND小鼠的葡萄糖清除率降低，LND小鼠的全身葡萄糖清除率降低。由于禁食的OBD小鼠是高胰岛素，瘦小鼠略微胰岛素，因此胰岛素水平与葡萄糖利用率增加之间没有相关性。在体内，在OBD小鼠的大多数肌肉中，通过2- [C-14]评估的葡萄糖摄取减少，但与对照小鼠的值相比，LND小鼠中的葡萄糖摄取量减少，但在LND小鼠中增加了。在LD小鼠中，伸肌长长（EDL）和总后肢的葡萄糖摄取率降低，但比目鱼，隔膜和心脏增加。当在体外评估时，在不存在和存在胰岛素的情况下，葡萄糖的利用率在所有小鼠中分离出的diaphragm，soleus和EDL肌肉中相似。因此，在遗传同质小鼠中，HFD喂养导致不同的代谢适应。尽管所有小鼠均具有胰岛素耐药性，但这与肥胖小鼠相关，葡萄糖清除率降低和高胰岛素血症，在瘦小的小鼠中，在存在温和胰岛素的情况下，葡萄糖清除率增加。因此，无法通过胰岛素水平升高来解释瘦小小鼠中增加的葡萄糖清除率，这表明其他体内机制也会触发以控制肌肉葡萄糖的利用。这些适应性机制可以参与防止肥胖发展的保护。
C57BL/6J mice were fed a high-fat, carbohydrate-free diet (HFD) for 9 mo. Approximately 50% of the mice became obese and diabetic (ObD), similar to10% lean and diabetic (LD), similar to10% lean and nondiabetic (LnD), and similar to30% displayed intermediate phenotype. All of the HFD mice were insulin resistant. In the fasted state, whole body glucose clearance was reduced in ObD mice, unchanged in the LD mice, and increased in the LnD mice compared with the normal-chow mice. Because fasted ObD mice were hyperinsulinemic and the lean mice slightly insulinopenic, there was no correlation between insulin levels and increased glucose utilization. In vivo, tissue glucose uptake assessed by 2-[C-14] deoxyglucose accumulation was reduced in most muscles in the ObD mice but increased in the LnD mice compared with the values of the control mice. In the LD mice, the glucose uptake rates were reduced in extensor digitorum longus (EDL) and total hindlimb but increased in soleus, diaphragm, and heart. When assessed in vitro, glucose utilization rates in the absence and presence of insulin were similar in diaphragm, soleus, and EDL muscles isolated from all groups of mice. Thus, in genetically homogenous mice, HFD feeding lead to different metabolic adaptations. Whereas all of the mice became insulin resistant, this was associated, in obese mice, with decreased glucose clearance and hyperinsulinemia and, in lean mice, with increased glucose clearance in the presence of mild insulinopenia. Therefore, increased glucose clearance in lean mice could not be explained by increased insulin level, indicating that other in vivo mechanisms are triggered to control muscle glucose utilization. These adaptive mechanisms could participate in the protection against development of obesity.