Clinical And Basic Research Of The Internal And External Factors Related To Lipid Metabolism-Climate And TSH

The first partEffects of Climatic Factors on Plasma Lipid Levels:A 5-year Longitudinal Study in A Large Chinese PopulationBackground:The rules and mechanisms of seasonal changes in plasma lipid levels, which may berelated to annual rhythmicity of incidence and mortality of cardiovascular diseases, are still controversial.Objective:To study the effects of climatic factors on plasma lipid levels and preliminarily reveal mechanisms of annual rhythmicity of plasma lipid levels.Methods:A longitudinal study was performed using health examination data of five consecutive years (47,270 subjects) in Jinan, China. The climate in Jinan is typical temperate continental monsoon climate with huge temperature difference between winter and summer (>30?).Results:After considering and adjusting those classical lipid-associated risk factors, such as age, sex, diet, exercise, blood pressure, body weight, change of body weight, BMI, glycemia, ALT and creatinine, only air temperature could still significantly affect plasma lipid levels among the main climatic factors (humidity, precipitation, etc.). For male, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) was decreased significantly 0.35, 0.18 and 0.06 mmol/L, respectively, while triglyceride (TG) was increased significantly 0.12 mmol/L for every 10? increase in air temperature. For female, TC and HDL-C were decreased notably 0.73 and 0.32 mmol/L and LDL-C was increased significantly 0.26 mmol/L for every 10? increase in air temperature, while TG was not significantly affected by air temperature. Conclusion:Air temperature is an independent risk factor for plasma lipid levels besides those classical lipid-associated risk factors. The annual air temperature fluctuations might be an important mechanism of the seasonal changes of lipids.The second partQuantitative proteomic analysis of liver of TSHR knockout mouse Background:More and more studies have found that thyroid stimulating hormone (TSH) may increase the triglyceride (TG) accumulation in hepatic cells, affect the synthesis and metabolism of cholesterol. But the related mechanism has not yet been fully elucidated. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) technology was uesed to reveal the different expression of liver at proteome level in TSHR knockout mice and control mice on the high fat diet 20 weeks. This study provide clues and direction for the functions of TSH in liver, especially its roles and regulation mechanism in the synthesis and metabolism of TC and TG in liver for further study.Purpose:This study focused on revealing the proteins and networks regulated by TSH in liver using quantitative proteomic technology in order to provide valuable clues and directions ways for the mechanisms of TSH impacting proteins mechanisms involved in lipid metabolism in the liver.Methods:Mouse liver protein samples were digested by trypsinafter protein concentration determination. Then, they were labeled by ITRAQ reagent and separated using high pH reverse phase chromatography and were analyzed by Nano LC-MS/MS. The tandem mass spectrometry data acquired were analyzed by Proteome Discoverer (Version 1.4) a searchable database software for protein identification, quantitation and difference analysis. The enrichment analysis of GO (gene ontology) and pathways (including KEGG) for these differentially expressed proteins were performed. The protein protein interaction networks were constructed and analyzed using Cytoscape software.Results:5173 proteins were identified, of which 5168 were quantified. Compared with the control group,109 proteins were up-regulated and 70 proteins were down-regulated in group of TSHR knockout mice. Based on GO database, the enrichment analysis showed that those differentially expressed proteins in TSHR knockout mice were involved in many important biological processes, such as cell cycle, proliferation and RNA splicing. Particularly, many of them were associated with the metabolism process including lipid metabolism and steroid hormone metabolism. This regult suggested that the function of TSH in the liver was mainly related to the biological processes of material metabolism, especially the lipid metabolism and steroid hormone metabolism. The interaction network was constructed based on the expression data of differentially expressed proteins in TSHR knockout mice. The results indicated that their interactions were very complex. The topological analysis of this large network was performed and it revealed some crucial nodes, which were involved in the biological processes similar to the results of enrichment analysis. Namely, the interaction networks regulated by TSHR were associated with lipid metabolism, cholesterol metabolism and steroid hormone metabolism.Conclusion:Many important functional proteins were regulated by TSH in liver. The most significant functions related to TSH were to regulate the lipid metabolism including synthesis and metabolism of TC and TG, cholesterol metabolism and steroid metabolism.