Transgenic fat-1 mouse as a model to study the pathophysiology of cardiovascular, neurological and psychiatric disorders
Transgenic fat-1 mouse as a model to study the pathophysiology of cardiovascular, neurological and psychiatric disorders
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转基因 fat-1 小鼠作为研究心血管、神经和精神疾病病理生理学的模型
DOI：
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发表时间：
2009
影响因子：
4.5
通讯作者：
Laszlo G. Puskas
中科院分区：
文献类型：
--
作者：
U. N. Das;Laszlo G. Puskas
多不饱和脂肪酸（PUFA）是人体所有细胞膜的重要组成部分。PUFA如花生四烯酸（AA）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）形成促炎和抗炎化合物的前体。低度全身性炎症发生在临床病症中，例如胰岛素抵抗、高血压、2型糖尿病、动脉粥样硬化、冠心病、狼疮、精神分裂症、阿尔茨海默病和其他痴呆、癌症和非酒精性脂肪肝疾病（NAFLD），其特征也在于以促炎性类花生酸的过量产生的形式的必需脂肪酸代谢的改变，并且可能，抗炎脂氧素、消退素、保护素和maresins的合成和释放减少。我们认为，在这些临床条件下观察到的低度全身性炎症是由于必需脂肪酸代谢的不平衡，更有利于促炎分子。在这种情况下，转基因fat-1小鼠，旨在转换n-6到n-3脂肪酸可以形成一个理想的模型，以研究在上述条件下的必需脂肪酸的代谢改变。据设想，在fat-1小鼠中，低度全身性炎性病症的可能性要小得多，和/或这些疾病将经历相对温和的过程。从n-3脂肪酸中鉴定出抑制低度全身性炎症的抗炎化合物，并了解其作用机制，可能会导致更新的治疗策略。
Polyunsaturated fatty acids (PUFAs) form an important constituent of all the cell membranes in the body. PUFAs such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) form precursors to both pro-inflammatory and anti-inflammatory compounds. Low-grade systemic inflammation occurs in clinical conditions such as insulin resistance, hypertension, type 2 diabetes mellitus, atherosclerosis, coronary heart disease, lupus, schizophrenia, Alzheimer's disease, and other dementias, cancer and non-alcoholic fatty liver disease (NAFLD) that are also characterized by an alteration in the metabolism of essential fatty acids in the form of excess production of pro-inflammatory eicosanoids and possibly, decreased synthesis and release of anti-inflammatory lipoxins, resolvins, protectins and maresins. We propose that low-grade systemic inflammation observed in these clinical conditions is due to an imbalance in the metabolism of essential fatty acids that is more in favour of pro-inflammatory molecules. In this context, transgenic fat-1 mouse that is designed to convert n-6 to n-3 fatty acids could form an ideal model to study the altered metabolism of essential fatty acids in the above mentioned conditions. It is envisaged that low-grade systemic inflammatory conditions are much less likely in the fat-1 mouse and/or these diseases will run a relatively mild course. Identifying the anti-inflammatory compounds from n-3 fatty acids that suppress low-grade systemic inflammatory conditions and understanding their mechanism(s) of action may lead to newer therapeutic strategies.
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影响因子：
3.1
作者：
Weiguo Wang;Scott L. Diamond
通讯作者：
Weiguo Wang;Scott L. Diamond
影响因子：
15.9
作者：
Lukiw, WJ;Cui, JG;Bazan, NG
通讯作者：
Bazan, NG
影响因子：
4.1
作者：
Field, FJ;Born, E;Mathur, SN
通讯作者：
Mathur, SN
DOI：
10.1073/pnas.0601280103
发表时间：
2006-07-25
影响因子：
11.1
作者：
Hudert, Christian A.;Weylandt, Karsten H.;Kang, Jing X.
通讯作者：
Kang, Jing X.
DOI：
10.1073/pnas.0502903102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Akbar, M;Calderon, F;Kim, HY
通讯作者：
Kim, HY