Cellular program controlling the recovery of adipose tissue mass:: An in vivo imaging approach
Cellular program controlling the recovery of adipose tissue mass:: An in vivo imaging approach
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DOI：
10.1073/pnas.0805621105
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发表时间：
2008-09-02
影响因子：
11.1
通讯作者：
Friedman, Jeffrey M.
中科院分区：
文献类型：
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作者：
Birsoy, Kivanc;Soukas, Alexander;Friedman, Jeffrey M.
细胞程序负责恢复脂肪组织质量后，体重减轻很大程度上是uncharacterized。瘦素mRNA水平与脂肪组织质量高度相关，因此瘦素表达可用作脂肪组织量变化的替代物。为了进一步研究脂肪细胞对体重变化的反应，我们建立了一个转基因小鼠，在瘦素调控序列的控制下表达荧光素酶报告基因，这允许在体内对小鼠瘦素表达进行非侵入性成像。我们使用这些动物来证明禁食或瘦素治疗引起的体重减轻导致脂质耗尽的脂肪细胞保留在脂肪库中。为了进一步研究瘦素治疗后对体重恢复的细胞反应，使用瘦素戒断方案在野生型小鼠中诱导急性瘦素缺乏状态。急性瘦素缺乏导致大量糖原在预先存在的脂质耗尽的脂肪细胞内瞬时沉积。随后是脂质的快速再积聚。转录谱分析显示，这种细胞反应与将葡萄糖转化为乙酰辅酶A和甘油（甘油三酯合成的关键底物）所必需的酶的整个途径的mRNA诱导相关。
The cellular program responsible for the restoration of adipose tissue mass after weight loss is largely uncharacterized. Leptin mRNA levels are highly correlated with adipose tissue mass, and leptin expression can thus be used as a surrogate for changes in the amount of adipose tissue. To further study the responses of adipocytes to changes in weight, we created a transgenic mouse expressing the luciferase reporter gene under the control of leptin regulatory sequences, which allows noninvasive imaging of the leptin expression of mice in vivo. We used these animals to show that weight loss induced by fasting or leptin treatment results in the retention of lipid-depleted adipocytes in adipose depots. To further study the cellular response to weight regain after leptin treatment, a leptin withdrawal protocol was used to induce a state of acute leptin deficiency in wild type mice. Acute leptin deficiency led to the transient deposition of large amounts of glycogen within pre-existing, lipid-depleted adipocytes. This was followed by rapid reaccumulation of lipid. Transcriptional profiling revealed that this cellular response was associated with induction of mRNAs for the entire pathway of enzymes necessary to convert glucose into acetyl-CoA and glycerol, key substrates for the synthesis of triglycerides.