SCFA and skeletal muscle substrate metabolism

The short-chain fatty acids (SCFA) acetate, propionate and butyrate can alter skeletal muscle metabolism both via direct and indirect mechanisms. Indirect mechanisms include the stimulation of glucagon like peptide 1 (GLP-1) and peptide YY (PYY) release via G-protein coupled receptor 41 (GPR41) and GPR43 signalling. Increased peripheral levels of these gut-derived satiety hormones induce the recruitment of microvasculature in skeletal muscle tissue and thereby contribute to improved insulin signalling. Furthermore SCFA induce a reduction in lipolysis in white adipose tissue (WAT), resulting in enhanced WAT lipid buffering capacity and decreased levels ectopic fat accumulation in skeletal muscle tissue. SCFA are also suggested to have direct effects on skeletal muscle metabolism, possibly via GPR41 and GPR43 signalling. SCFA induce the activation of adenosine monophosphate-activated protein kinase (AMPK), a key regulator in skeletal muscle cell metabolism. Activated AMPK induces several metabolic pathways including fatty acid oxidation and the synthesis of glycogen. Active AMPK also stimulates glucose uptake via translocation of glucose transporter type 4 (GLUT4) and decreases glycolysis. In addition to AMPK activation, SCFA might also induce peroxisome proliferator activated receptor delta (PPARD) expression, another process contributing to enhanced fat oxidation levels.

短链脂肪酸（SCFA），包括乙酸、丙酸和丁酸，能够通过直接和间接机制改变骨骼肌的代谢。间接机制包括通过G蛋白偶联受体41（GPR41）和GPR43信号传导途径刺激胰高血糖素样肽-1（GLP-1）和肽YY（PYY）的释放。这些源自肠道的外周饱和激素水平增加，诱导骨骼肌组织中微血管的招募，从而有助于改善胰岛素信号传导。此外，SCFA还能够减少白色脂肪组织（WAT）中的脂肪分解，从而增强WAT的脂质缓冲能力，并降低骨骼肌组织中异位脂肪积累的水平。SCFA还被认为对骨骼肌代谢具有直接作用，可能通过GPR41和GPR43信号传导途径实现。SCFA可诱导腺苷酸单磷酸激活蛋白激酶（AMPK）的激活，它是骨骼肌细胞代谢的关键调节因子。激活的AMPK可诱导包括脂肪酸氧化和糖原合成的多种代谢途径。活跃的AMPK还通过葡萄糖转运蛋白4（GLUT4）的转位刺激葡萄糖的摄取，并降低糖酵解。除了AMPK的激活，SCFA还可能诱导过氧化物酶体增殖激活受体δ（PPARD）的表达，这一过程也有助于提高脂肪氧化水平。