The Role of cAMP-PKA Pathway in Lactate-Induced Intramuscular Triglyceride Accumulation and Mitochondria Content Increase in Mice.
The Role of cAMP-PKA Pathway in Lactate-Induced Intramuscular Triglyceride Accumulation and Mitochondria Content Increase in Mice.
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cAMP-PKA 通路在乳酸诱导的小鼠肌内甘油三酯积累和线粒体含量增加中的作用
DOI：
10.3389/fphys.2021.709135
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发表时间：
2021
影响因子：
4
通讯作者：
Chen M
中科院分区：
文献类型：
--
作者：
Chen S;Zhou L;Sun J;Qu Y;Chen M
运动的糖酵解产物乳酸，通过激活g蛋白偶联受体81 （GPR81）和抑制脂肪组织中环腺苷单磷酸蛋白激酶A （cAMP -PKA）通路，促进脂质积累。乳酸是否在骨骼肌中引起类似的过程尚不清楚。乳酸也可能提高骨骼肌中线粒体的含量；然而，其机制也不清楚。在这项研究中，我们通过肌内注射乳酸到腓骨和腹腔注射福斯克林（cAMP-PKA通路的激活剂），我们确定了cAMP-PKA通路在乳酸诱导的肌内甘油三酯积累和线粒体含量增加中的作用。乳酸注射液5周后腓肠肌内甘油三酯水平升高（p<0.05），而福斯克林注射液可阻断这种作用（p<0.05）。GPR81、P-PKA/PKA、P-CREB/ camp反应元件结合蛋白（CREB）及脂质代谢相关蛋白的表达水平变化表明，乳酸部分通过抑制cAMP-PKA通路诱导肌内甘油三酯积累。乳酸注射5周后肌内柠檬酸合成酶（citrate synthase， CS）表达及活性升高（p<0.05），但注射福斯克林并没有阻断CS表达的变化，可能存在其他机制。因此，对可能导致乳酸诱导的线粒体含量增加的其他潜在机制进行了探索。我们发现急性注射乳酸后骨骼肌线粒体中乳酸相关代谢物含量增加（各分析p值均小于0.05）。本研究也证实了LHDA存在于线粒体中。这些结果为乳酸诱导线粒体含量增加的代谢相关机制提供了可能。需要进一步的研究来验证这一假设。综上所述，乳酸诱导的肌内甘油三酯积累是通过抑制脂肪分解来实现的，这一过程受cAMP-PKA通路的调节。促进脂肪生成也有助于乳酸诱导的甘油三酯积累，这一过程也可能受到cAMP-PKA途径的调节。乳酸注射液可能增加线粒体含量，cAMP-PKA通路可能贡献有限，其他代谢相关机制可能发挥突出作用。
The glycolytic product of exercise, lactate, has long been recognized to promote lipid accumulation by activation of G-protein-coupled receptor 81 (GPR81) and inhibition of the cyclic adenosine monophosphate-protein kinase A (cAMP –PKA) pathway in adipose tissue. Whether lactate causes a similar process in skeletal muscle is unclear. Lactate might also improve mitochondria content in skeletal muscle; however, the mechanism is not clarified either. In this study, using intramuscular injection of lactate to the gastrocnemius and intraperitoneal injection of forskolin (activator of cAMP-PKA pathway), we identified the role of the cAMP-PKA pathway in lactate-induced intramuscular triglyceride accumulation and mitochondrial content increase. The intramuscular triglyceride level in the gastrocnemius increased after 5weeks of lactate injection (p<0.05), and this effect was blocked by forskolin injection (p<0.05). Corresponding expression level changes of GPR81, P-PKA/PKA, P-CREB/cAMP-response element binding protein (CREB), and proteins related to lipid metabolism suggest that lactate could induce intramuscular triglyceride accumulation partly through the inhibition of the cAMP-PKA pathway. Meanwhile, the intramuscular expression of citrate synthase (CS) and the activity of CS increased after 5weeks of lactate injection (p<0.05), but the change of CS expression was not blocked by forskolin injection, suggesting other mechanisms might exist. Consequently, exploration for other potential mechanisms that might contribute to the lactate-induced mitochondria content increase was conducted. We found an increase in the contents of lactate-related metabolites in skeletal muscle mitochondria after acute lactate injection (the p-value of each analysis is less than 0.05). LHDA was also validated to exist in mitochondria in this study. These results provide a possibility for metabolism-related mechanisms of lactate-induced mitochondria content increase. Future study is needed to validate this hypothesis. In conclusion, lactate-induced intramuscular triglyceride accumulation is achieved by inhibition of lipolysis, and this process is regulated by the cAMP-PKA pathway. Promoted lipogenesis also contributes to lactate-induced triglyceride accumulation, and this process might also be regulated by the cAMP-PKA pathway. Lactate injection might increase mitochondria content and cAMP-PKA pathway might have a limited contribution, while other metabolism-related mechanisms might play a prominent role.
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影响因子：
4.6
作者：
Nederlof R;van den Elshout MAM;Koeman A;Uthman L;Koning I;Eerbeek O;Weber NC;Hollmann MW;Zuurbier CJ
通讯作者：
Zuurbier CJ
DOI：
10.1016/j.bbamcr.2014.10.016
发表时间：
2015-01-01
影响因子：
5.1
作者：
De Rasmo, Domenico;Signorile, Anna;Papa, Sergio
通讯作者：
Papa, Sergio
影响因子：
7.4
作者：
De Rasmo, Domenico;Signorile, Anna;Papa, Sergio
通讯作者：
Papa, Sergio
影响因子：
5.8
作者：
Bogacka, I;Ukropcova, B;Smith, SR
通讯作者：
Smith, SR
影响因子：
3.9
作者：
Brownsey, RW;Boone, AN;Lee, WM
通讯作者：
Lee, WM