Wang Minghui, Jiao Hongchao, Zhao Jingpeng, Lin Hai, Wang Xiaojuan
Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science & Technology, Shandong Agricultural University, Taian, China.
Front Vet Sci. 2022 Jul 15;9:965894. doi: 10.3389/fvets.2022.965894. eCollection 2022.
Fatty acid transport protein 1 (FATP1), plays a major role in the transport and uptake of fatty acids into cells. The effect of FATP1 on the regulation of skeletal muscle fat uptake and deposition in stressed broiler chickens was investigated both and , and the effect of different fatty acid substrates were also included. Dexamethasone (DEX), a synthetic glucocorticoid (GCs), was employed to induce a hyper glucocorticoid milieu and simulate stress. The results showed that DEX would increase the mRNA expression of FATP1 and fat deposition in muscle tissues ( < 0.05), the very-low-density lipoprotein (VLDL) and insulin (INS) levels were significantly increased in the plasma by DEX ( < 0.05), and the mRNA levels of the glucocorticoid receptor (), adiponectin receptor () and peroxisomal proliferator-activated receptor α (α) in thigh were also up-regulated by DEX ( < 0.05). experiment, DEX did not affect the myoblast fat deposition and α and expressions without the external fatty acid ( > 0.05). Under PA pre-treatment, both myoblast fatty acid uptake and fat deposition were promoted by DEX treatment ( < 0.05), and the effects of DEX on the gene expressions of α and were upregulated first and then downregulated as the dose of DEX increases; while under OA pre-treatment, the myoblast fat deposition was not affected by DEX ( > 0.05), the fatty acid uptake was decreased by DEX at 500 nM compared to control ( < 0.05). When GR and PPARα were, respectively inhibited by specific inhibitors RU486 and GW6471, the effects of DEX on fatty acid uptake were reversed for PA pre-treated myoblasts ( < 0.05) but not for OA pre-treated myoblasts ( > 0.05). These results indicate that FATP1 regulation by GCs was affected by fatty acid substrate - saturated fatty acids were favorable for fat uptake and deposition, while unsaturated fatty acids were not. GCs may affect the ADPNR-PPARα-FATP1 pathway by binding to its receptors, thus regulating the uptake of saturated fatty acids into myoblasts.
脂肪酸转运蛋白1(FATP1)在脂肪酸转运进入细胞以及细胞摄取脂肪酸过程中发挥着主要作用。本研究对FATP1在应激肉鸡骨骼肌脂肪摄取和沉积调节中的作用进行了体内和体外研究,同时也纳入了不同脂肪酸底物的影响。地塞米松(DEX)是一种合成糖皮质激素(GCs),被用于诱导高糖皮质激素环境并模拟应激。结果表明,DEX会增加FATP1的mRNA表达以及肌肉组织中的脂肪沉积(P<0.05),DEX使血浆中极低密度脂蛋白(VLDL)和胰岛素(INS)水平显著升高(P<0.05),并且大腿中糖皮质激素受体(GR)、脂联素受体(ADPNR)和过氧化物酶体增殖物激活受体α(PPARα)的mRNA水平也被DEX上调(P<0.05)。体外实验中,在没有外源性脂肪酸的情况下,DEX不影响成肌细胞脂肪沉积以及GR和PPARα的表达(P>0.05)。在棕榈酸(PA)预处理下,DEX处理促进了成肌细胞脂肪酸摄取和脂肪沉积(P<0.05),并且随着DEX剂量增加,DEX对GR和PPARα基因表达的影响先上调后下调;而在油酸(OA)预处理下,DEX不影响成肌细胞脂肪沉积(P>0.05),与对照组相比,500 nM的DEX使脂肪酸摄取减少(P<0.05)。当GR和PPARα分别被特异性抑制剂RU486和GW6471抑制时,对于PA预处理的成肌细胞,DEX对脂肪酸摄取的影响被逆转(P<0.05),但对于OA预处理的成肌细胞则未被逆转(P>0.05)。这些结果表明,GCs对FATP1的调节受脂肪酸底物影响——饱和脂肪酸有利于脂肪摄取和沉积,而不饱和脂肪酸则不然。GCs可能通过与其受体结合影响ADPNR-PPARα-FATP1通路,从而调节饱和脂肪酸进入成肌细胞的摄取。