title: Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach.
abstract: Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I2 and decreased PGE2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A2, as indicated by TXB2, in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China; Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Rina
authors.initials: R
authors.lastname: Sa
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ye
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Xia
authors.affiliation: Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Nutrition, Shanghai Xuhui Central Hospital, Shanghai 200031, China.
authors.forename: Yu-cheng
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China. Electronic address: hyyin@sibs.ac.cn.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Yin
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China; Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: yinghao@sibs.ac.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
mesh_terms: D000328:Adult; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood*; D001794:Blood Pressure; D015232:Dinoprostone / Q000097:blood; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood* / Q000503:physiopathology; D007037:Hypothyroidism / Q000097:blood* / Q000503:physiopathology; D019787:Linoleic Acid / Q000097:blood; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D013929:Thromboxane B2 / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood*; D055815:Young Adult
chemical_list: D013963:Thyroid Hormones; D016718:Arachidonic Acid; D013929:Thromboxane B2; D019787:Linoleic Acid; D015232:Dinoprostone
keywords: Arachidonic acid metabolites; Cardiovascular disorders; Hyperthyroidism; Hypothyroidism; Targeted metabolomic approach