Temporal and regional onset of leptin resistance in diet‐induced obese mice
Temporal and regional onset of leptin resistance in diet‐induced obese mice
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饮食诱导的肥胖小鼠瘦素抵抗的时间和区域发作
DOI：
10.1111/jne.12481
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发表时间：
2017
影响因子：
3.2
通讯作者：
Tups A
中科院分区：
文献类型：
--
作者：
Rizwan MZ;Mehlitz S;Grattan DR;Tups A
在常见的肥胖形式中，瘦素未能传达其调节作用。这种所谓的“瘦素抵抗”还没有被很好地理解，而解决这个谜题是理解肥胖是如何发展的关键。在目前的研究中，我们调查了小鼠对富含长链饱和脂肪酸的饮食(高脂肪饮食；HFD)的反应而出现瘦素抵抗的时间和区域。小鼠被暴露于低脂饮食(LFD)或高脂饮食(HFD)4小时、24小时、10天和28天。每组小鼠均接受一次ip。分别于注射磷酸盐缓冲液或瘦素后30分钟和120分钟，分析下丘脑弓状核(ARC)、下丘脑腹内侧核(VMH)和下丘脑背内侧核(DMH)内磷酸化信号转导和转录激活剂3(PSTAT3)免疫反应细胞的数量。在ARC中，高脂饮食后24小时，分子瘦素反应就下降了40%(P≤.01)。与24小时相比，10天后，120分钟后瘦素诱导的pSTAT3-IR细胞数量增加，表明瘦素持续反应和部分恢复瘦素敏感性。28天后，瘦素未能诱导pSTAT3-IR的数量超过对照水平，这表明对瘦素的敏感性显著降低。在24小时后的VMH，我们观察到瘦素诱导的pSTAT-3-IR细胞减少了50%，10天后进一步下降。但28天后，pSTAT-3-IR细胞明显增多(P≤.05)，表明瘦素敏感性部分恢复。与这两个区域相比，在DMH中，在任何时间点都没有观察到瘦素敏感性的丧失。这些发现表明，暴露于HFD后，ARC和VMH对瘦素的敏感性迅速下降，但DMH没有。然而，瘦素的反应性似乎有一个双相模式，在弓状核中10天后部分恢复瘦素敏感性，在VMH中在28天后部分恢复瘦素敏感性。到28天时，弓状核对瘦素的反应完全消失。这些发现表明，在高脂肪喂养后，瘦素的分子反应会以特定时间和地区的方式发生变化。
In common forms of obesity, leptin fails to convey its regulatory effect. This so called “leptin resistance” is not well understood, and solving this puzzle is a key to understanding how obesity develops. In the present study, we investigated the temporal and regional onset of leptin resistance in response to a diet enriched with long‐chain saturated fatty acids (high‐fat diet; HFD) in mice. Mice were exposed to either a low‐fat diet (LFD) or a HFD for 4 hours, 24 hours, 10 days and 28 days. Mice in each group received an i.p. injection of either phosphate‐buffered saline or leptin and the number of phosphorylated signal transducer and activator of transcription‐3 (pSTAT3) immunoreactive (‐IR) cells in the arcuate nucleus (ARC), ventromedial nucleus of the hypothalamus (VMH) and dorsomedial nucleus of the hypothalamus (DMH) was analysed 30 or 120 minutes after treatment. In the ARC, as soon as 24 hours of HFD, the molecular leptin response was reduced by 40% (P≤.01). Compared to at 24 hours, after 10 days, the number of leptin‐induced pSTAT3‐IR cells was elevated after 120 minutes, suggesting a sustained response and a partial return of leptin sensitivity. After 28 days, leptin failed to induce the number of pSTAT3‐IR over control levels, suggesting a markedly reduced sensitivity to leptin. In the VMH after 24 hours, we observed a 50% reduction in leptin‐induced pSTAT‐3‐IR cells, followed by a further decline after 10 days. However, after 28 days, there was a significant increase in pSTAT‐3‐IR cells (P≤.05), indicating partial recovery of leptin sensitivity. By contrast to these two regions, in the DMH, no loss of leptin sensitivity was observed at any time‐point. These findings demonstrate that a loss of sensitivity to leptin occurs rapidly after exposure to HFD in the ARC and VMH but not the DMH. However, there appears to be a biphasic pattern of leptin responsiveness, with a partial return of leptin sensitivity occurring after 10 days in the arcuate nucleus, and after 28 days in the VMH. By 28 days, the response to leptin in the arcuate nucleus was completely lost. These findings suggest that the molecular responses to leptin are altered after high‐fat feeding in a time‐ and region‐specific manner.
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影响因子：
3.2
作者：
A. Tups;P. Barrett;A. Ross;Peter J. Morgan;Martin Klingenspor;Julian G. Mercer
通讯作者：
A. Tups;P. Barrett;A. Ross;Peter J. Morgan;Martin Klingenspor;Julian G. Mercer
DOI：
10.1007/s00360-011-0637-4
发表时间：
2012-05
期刊：
Journal of Comparative Physiology B
影响因子：
--
作者：
A. Tups;S. Stöhr;M. Helwig;P. Barrett;E. Król;J. Schachtner;J. Mercer;M. Klingenspor
通讯作者：
A. Tups;S. Stöhr;M. Helwig;P. Barrett;E. Król;J. Schachtner;J. Mercer;M. Klingenspor
影响因子：
15.9
作者：
Thaler, Joshua P.;Yi, Chun-Xia;Schwartz, Michael W.
通讯作者：
Schwartz, Michael W.
影响因子：
15.9
作者：
Haynes, WG;Morgan, DA;Sivitz, WI
通讯作者：
Sivitz, WI
影响因子：
4.8
作者：
Faouzi, Miro;Leshan, Rebecca;Muenzberg, Heike
通讯作者：
Muenzberg, Heike