棕色脂肪组织中脂滴与线粒体互作调控丙酮酸氧化、ATP产生和甘油三酯的合成，在产热功能和能量代谢中发挥重要作用。已知PKM2激酶调控糖酵解、细胞凋亡和增殖，但其在脂肪组织中的代谢功能还不完全清楚。我们的研究发现PKM2与脂滴-线粒体互作关键蛋白Plin5相互作用，敲低PKM2增加脂滴与线粒体互作，并促进棕色脂肪细胞分化。基于前期数据，我们推断PKM2激酶通过磷酸化Plin5调控其细胞定位，抑制脂滴与线粒体互作，进而负调控棕色脂肪产热功能。为深入研究PKM2的代谢调控机制，本项目计划：1）使用棕色前脂肪细胞研究PKM2通过靶标Plin5调控脂滴与线粒体互作的机制，并揭示其在代谢调节中的潜在作用；2）构建棕色脂肪pkm2敲除小鼠，研究PKM2在脂肪组织中的生理功能。本项目将明确PKM2抑制脂滴与线粒体互作的机制及其在脂肪组织中的生理功能，为治疗肥胖和糖尿病提供理论基础。

The interaction between lipid droplets (LDs) and mitochondria in brown adipose tissue regulates the levels of pyruvate oxidation, ATP production and triglyceride synthesis, and play important roles in thermogenesis and energy metabolism. PKM2 regulates glycolysis, apoptosis and proliferation, but its roles in metabolic function of adipose tissue are poorly understood. Our previous study shown that PKM2 in brown adipocytes may regulate the interaction of LDs and mitochondria through binding to Plin5, knockdown of PKM2 enhances the interaction between LDs and mitochondria, and also promotes the differentiation of pre-brown adipocyte cell. We propose the hypothesis: PKM2 kinase phosphorylates Plin5 and changes its location, thus inhibiting the interaction between LDs and mitochondria to negatively regulate brown adipose thermogenic function. In order to further study the metabolic function of PKM2, our project plan to: 1) use pre-brown adipocyte cell line (BFC) to investigate the mechanism of PKM2 target Plin5 to regulate LDs and mitochondria interaction; 2) generate brown adipocyte specific pkm2 deletion mice pkm2flox/flox-ucp1-Cre to determine the Physiological Function. This project will clarify the specific mechanism and physiological function of PKM2 in inhibiting the interaction between mitochondria and LDs, which provide theoretical basis for the development of new methods to treat obesity and diabetes.