肝分泌因子调节脂肪组织代谢的分子机制与生物学功能

肝分泌因子调节脂肪组织代谢的分子机制与生物学功能

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批准号：31430044

批准年度：2014年

学科分类：整合生理（C1109） |

项目负责人：宋保亮

负责人职称：教授

依托单位：武汉大学

资助金额：317万元

项目类别：重点项目

研究期限：2015年01月01日 至 2019年12月31日

中文关键词：因子；脂肪；组织；代谢；生物学

英文关键词：cholesterol metabolism;fatty liver;energy homeostasis;fat;hepatokine

项目摘要

中文摘要

代谢过程除在细胞内受调控外，还受组织器官之间通讯的调节。肝脏是脂质合成、转化和分泌的主要器官；而脂肪则负责脂质储存与氧化，二者之间的互作非常紧密。我们发现，gp78肝脏特异性敲除小鼠，除肝内脂质合成减少外，还表现为白色脂肪组织脂肪酸合成增加，棕色脂肪中UCP1表达增加，产热增强，部分原因是由于肝脏分泌FGF21增多。同时，我们用脂质合成抑制剂白桦酯醇处理小鼠，降低肝脏脂质水平，也可导致棕色脂肪产热增加。这些结果均表明肝脏脂质代谢改变后，可通过分泌不同因子，调控脂肪组织。但是，只有少数肝分泌因子被发现，肝脏—脂肪互作的机制还所知甚少。本项目将利用小鼠模型，系统性筛选受脂质水平调控的肝分泌因子，揭示它们对脂肪组织的调节作用。探索在肝脏中其表达受脂质水平调节的机理，以及它们对脂肪细胞分化成熟、脂质代谢和能量代谢的调控机制。并利用疾病模型小鼠研究这些肝分泌因子在脂肪肝、肥胖和糖尿病等发生中的作用。

英文摘要

Metabolic processes are tightly controlled in cells. They are also regulated through organ-organ communication. Liver is the major organ for lipid biosynthesis, conversion and secretion. Fat is responsible for the storage and oxidation of lipid. The interaction between liver and fat tissues is intimate and important. We have found that in the gp78 liver-specific knockout mice, lipid biosynthesis in liver decreases. However the synthesis of fatty acid in white adipose tissue increases. The expression of UCP1 in brow adipocytes is upregulated and the energy expenditure elevates. These phenomena are partially due to the increasing secretion of FGF21 in liver. We have also found betulin that inhibits lipid biosynthesis in liver causes the elevation of heat production in brown adipose tissue. Together, these results indicate that liver can regulate adipose tissue through producing hepatokines under different lipid levels. However, only a few hepatokines have been identified and the mechanism of liver-fat communication is poorly understood. This proposal will systematically screen and identify the hepatokines whose expression is regulated by lipid level and reveal their functions on regulating adipose tissues. We will investigate the mechanisms of their expression regulated by lipid in liver and their effects on the differentiation of pre-adipocytes and lipid and energy metabolism in adipose tissues. In addition, the roles of these hepatokines in fatty liver, obesity and type 2 diabetes will be investigated.

评估说明

国家自然科学基金项目“肝分泌因子调节脂肪组织代谢的分子机制与生物学功能”发布于爱科学iikx，并永久归类于相关科学基金导航中，仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划，以及科学技术发展方向，面向全国资助基础研究和应用研究，发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。