Institute of Sports Science, Sichuan University, Chengdu, China PR.
J Biol Regul Homeost Agents. 2021 Jan-Feb;35(1):105-115. doi: 10.23812/20-624-A.
Regular exercise induces intramuscular triglyceride accumulation with improved mitochondrial ability, but the mechanism remains unknown. The glycolytic product of exercise, lactate, has long been rec-ognized to suppress lipolysis and promote lipogenesis in adipocytes through inhibition of the cAMP-PKA pathway by activation of the G protein-coupled receptor (GPR81). However, whether lactate results in a similar process in skeletal muscle is unclear. Here, by using intramuscular injection of lactate to the gastrocnemius, the lipid metabolism effects were investigated in rat skeletal muscle. Firstly, the lactate-injection effect was verified by comparing changes in blood lactate levels from injection and exercise (30 min, 31 m/min, treadmill running). After five weeks of lactate intervention, intramuscular triglyceride levels in the gastrocnemius and the proportion of epididymis adipose mass to body weight increased. Chronic intramuscular injection of lactate elevated lactate receptor, GPR81, and reduced cAMP response element-binding (CREB) and P-CREB abundance in the gastrocnemius. Additionally, there was a significant decline in lipolytic-related proteins (AMPK, P-AMPK, P-HSL, CPT-1B, TGF-β2, SDHA) and a significant increase in fat synthesis proteins (SREBP-1C, PPAR-γ). Surprisingly, mitochondrial biomarkers (PGC-1α, CS) were also increased in the gastrocnemius, suggesting that chronic lactate might promote mitochondria biogenesis. Together, these results demonstrated that lactate may play a crucial role in triglyceride storage and mitochondria biogenesis in the skeletal muscle of rat.
规律运动可引起肌内甘油三酯积累，同时提高线粒体能力，但具体机制尚不清楚。运动产生的糖酵解产物——乳酸，长期以来一直被认为通过激活 G 蛋白偶联受体（GPR81）抑制 cAMP-PKA 通路，从而抑制脂肪细胞的脂解作用并促进脂肪生成。然而，乳酸是否会导致骨骼肌产生类似的过程尚不清楚。在这里，我们通过向大鼠腓肠肌肌内注射乳酸，研究了乳酸在骨骼肌中的脂质代谢作用。首先，通过比较注射和运动（30 min，31 m/min，跑步机跑步）后血液中乳酸水平的变化，验证了乳酸注射的效果。经过五周的乳酸干预，腓肠肌肌内甘油三酯水平和附睾脂肪质量与体重的比例增加。慢性腓肠肌内注射乳酸会升高乳酸受体 GPR81，并降低腓肠肌中的 cAMP 反应元件结合蛋白（CREB）和 P-CREB 丰度。此外，与脂肪分解相关的蛋白（AMPK、P-AMPK、P-HSL、CPT-1B、TGF-β2、SDHA）显著减少，而脂肪合成蛋白（SREBP-1C、PPAR-γ）显著增加。令人惊讶的是，腓肠肌中的线粒体生物标志物（PGC-1α、CS）也增加了，这表明慢性乳酸可能促进线粒体生物发生。综上所述，这些结果表明，乳酸可能在大鼠骨骼肌中甘油三酯储存和线粒体生物发生中起关键作用。
