）在线发表了中科院上海生命科学研究院营养所乐颖影研究组与秦莹研究组的合作研究论文Regulation of fasting fuel metabolism by Toll-like receptor 4。该项工作主要由乐颖影研究组博士研究生庞珊珊等完成。
在饥饿条件下，哺乳动物体内发生一系列适应性代谢应答以维持机体内环境稳态，但其中的分子机制尚不完全清楚。Toll-like receptor 4（TLR4）是免疫系统中的一个重要分子，最近的研究表明，TLR4介导的炎症反应在肥胖及糖尿病发生中起重要作用，然而，尚不清楚TLR4是否参与生理性代谢反应。
Diabetes. PMID: 20855545
Regulation of fasting fuel metabolism by Toll-like receptor 4.
Pang S, Tang H, Zhuo S, Zang YQ, Le Y.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Graduate School of Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai, 200031, China.
AbstractObjective - Toll-like receptor 4 (TLR4) has been reported to induce insulin resistance through inflammation in high-fat-fed mice. However, the physiological role of TLR4 in metabolism is unknown. Here, we investigate the involvement of TLR4 in fasting metabolism. Research design and methods - Wild-type (WT) and TLR4 deficient (TLR4-/-) mice were either fed or fasted for 24 hours. Glucose and lipid levels in circulation and tissues were measured. Glucose and lipid metabolism in tissues, as well as the expression of related enzymes, were examined. Results - Mice lacking TLR4 displayed aggravated fasting hypoglycemia, along with normal hepatic gluconeogenesis, but reversed activity of pyruvate dehydrogenase complex (PDC) in skeletal muscle, which might account for the fasting hypoglycemia. TLR4-/- mice also exhibited higher lipid levels in circulation and skeletal muscle after fasting, and reversed expression of lipogenic enzymes in skeletal muscle but not liver and adipose tissue. Adipose tissue lipolysis is normal and muscle fatty acid oxidation is increased in TLR4-/- mice after fasting. Inhibition of fatty acid synthesis in TLR4-/- mice abolished hyperlipidemia, hypoglycemia and PDC activity increase, suggesting that TLR4-dependent inhibition of muscle lipogenesis may contribute to glucose and lipid homeostasis during fasting. Further studies showed that TLR4 deficiency had no effect on insulin signaling and muscle proinflammatory cytokine production in response to fasting. Conclusions - These data suggest that TLR4 plays a critical role in glucose and lipid metabolism independent of insulin during fasting, and identify a novel physiological role for TLR4 in fuel homeostasis.