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Exposure to Oxidized Tyrosine Products Induced Glycometabolism Disorder Involving Thyroid Hormones Resistance in C57BL/6 mice
Author(s) -
Ding Yinyi,
Li Zhuqing,
Ran Yumei,
Shi Yonghui,
Le Guowei
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.976.3
Subject(s) - medicine , endocrinology , thyroid , hormone , tyrosine , downregulation and upregulation , chemistry , insulin resistance , hypothalamic–pituitary–thyroid axis , carbohydrate metabolism , hypothalamus , biology , insulin , thyroid hormones , biochemistry , gene
Oxidative modifications of aromatic amino acids can be easily found in protein‐riched food, such as meat and milk products. Tyrosine is one of the most easily oxidized amino acids, leading to formation of dityrosine, 3‐nitrotyrosine, and 3‐chlorotyrosine. Although many researches has started to focus on the protein oxidation in meat and dairy products, the influence of dietary oxidized protein on metabolic disturbance has not been fully explored. Thyroid hormones (THs) are widely known for their ability to influence various cellular processes. Previous studies demonstrated that thyroid hormone resistance (RTH) is associated with impairment of glucose metabolism. This study was to determine whether oxidized tyrosine products (OTPs) exposure could inhibit the thyroid hormone action in pancreas leading to glucose metabolism disorder. We found that OTPs exposure (640 μg/kg bw/day, 10 weeks) induced increased blood glucose and decreased plasma insulin content in C57BL/6 mice. These data reflected glucose metabolism disorder in OTPs mice. OTPs induced elevated plasma free THs in the presence of unsuppressed thyroid stimulating hormone (TSH) level. OTPs also altered mRNA levels of HPT‐axis related genes in hypothalamus, pituitary, and thyroid gland and histopathological data of thyroid gland. These data reflected that OTPs induced the resistance of THs to the normal negative feedback mechanism in the hypothalamus and pituitary, which is the character of RTH. The downregulation of membrane transporter of THs ( MCT8 ) and protein level of thyroid hormone receptor β1 (TRβ1) illustrated the decreased sensitivity to THs in pancreas. In addition, lower mRNA level of TRs co‐activator factors ( RXRα , Src‐1 ) in pancreas suggested the activation ability of THs to downstream gene involved in insulin synthesis ( MafA ) was suppressed by OTPs. Taken together, these findings suggested that OTPs triggers glucose metabolism disorder via thyroid hormone resistance in pancreas. To the best of our knowledge, this study is the first time to demonstrate that OTPs exposure is a risk factor of RTH in pancreas and inhibits insulin secretion. Support or Funding Information This research was supported by program of “Collaborative innovation center of food safety and quality control in Jiangsu Province”, the National Natural Science Foundation of China (No. 31571841), State Key Laboratory of Food Science and Technology of Jiangnan University in China (SKLF‐ZZB‐201609).