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从成年小鼠下丘脑建立瘦素反应性细胞系。

Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus.

作者信息

Iwakura Hiroshi, Dote Katsuko, Bando Mika, Koyama Hiroyuki, Hosoda Kiminori, Kangawa Kenji, Nakao Kazuwa

机构信息

Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

PLoS One. 2016 Feb 5;11(2):e0148639. doi: 10.1371/journal.pone.0148639. eCollection 2016.

DOI:10.1371/journal.pone.0148639
PMID:26849804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4744015/
Abstract

Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug-target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus-derived cell lines, termed adult mouse hypothalamus (AMH) cells, by developing transgenic mice in which SV40 Tag was overexpressed in chromogranin A-positive cells in a tamoxifen-dependent manner. In order to obtain leptin-responsive clones, we selected clones based on the phosphorylation levels of STAT3 induced by leptin. The selected clones were fairly responsive to leptin in terms of STAT3, ERK, and Akt phosphorylation and induction of c-Fos mRNA induction. Pretreatment with leptin, insulin, and palmitate attenuated the c-Fos mRNA response to leptin, suggesting that certain aspects of leptin resistance might be reconstituted in this cellular model. These cell lines are useful tools for understanding the molecular nature of the signal disturbance in the leptin-resistant state and for identifying potential target molecules for drugs that relieve leptin resistance, although they have drawbacks including de-differentiated nature and lack of long-time stability.

摘要

瘦素抵抗被认为是肥胖的主要原因。然而，瘦素抵抗的原因仍未完全明确，目前尚无治愈瘦素抵抗状态的方法。为了鉴定能够克服瘦素抵抗的新型药物靶点分子，开发评估瘦素抵抗的体外检测系统将很有帮助。在本研究中，我们通过构建转基因小鼠，使SV40 Tag在嗜铬粒蛋白A阳性细胞中以他莫昔芬依赖的方式过表达，从而建立了永生化的成年小鼠下丘脑来源细胞系，称为成年小鼠下丘脑（AMH）细胞。为了获得对瘦素有反应的克隆，我们根据瘦素诱导的STAT3磷酸化水平选择克隆。所选克隆在STAT3、ERK和Akt磷酸化以及c-Fos mRNA诱导方面对瘦素反应良好。用瘦素、胰岛素和棕榈酸预处理减弱了c-Fos mRNA对瘦素的反应，这表明在该细胞模型中可能重建了瘦素抵抗的某些方面。这些细胞系是理解瘦素抵抗状态下信号紊乱分子本质以及鉴定缓解瘦素抵抗药物潜在靶点分子的有用工具，尽管它们存在包括去分化性质和缺乏长期稳定性等缺点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/95aca3c11361/pone.0148639.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/213944ebf8c8/pone.0148639.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/b3a0c7e5ac19/pone.0148639.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/6ffc6563ec75/pone.0148639.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/669d34cdfad2/pone.0148639.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/eaa7c210329f/pone.0148639.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/95aca3c11361/pone.0148639.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/213944ebf8c8/pone.0148639.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/b3a0c7e5ac19/pone.0148639.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/6ffc6563ec75/pone.0148639.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/669d34cdfad2/pone.0148639.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/eaa7c210329f/pone.0148639.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1cc/4744015/95aca3c11361/pone.0148639.g006.jpg

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