Indole-3-propionic acid enhances glycolytic myofiber formation in piglets through PI3K-mTOR activation and gut microbiota-driven tryptophan metabolic alteration
Yezi Kong, Qi Wang, Jing Wang, Xiaoyu Qiu, Yong Yang, Jingbo Liu, Feiyun Yang, Renli Qi
Abstract
Indole-3-propionic acid (IPA) is a metabolite of tryptophan produced by gut bacterial catabolism that has a variety of functions, including anti-inflammatory, free radical scavenging, and regulation of glucose metabolism. The present study evaluated the effects of dietary IPA supplementation on early muscle development in piglets. Twelve healthy Landrace × Rongchang piglets at 30 d of age were randomly divided into control (CON group, 10.78 ± 0.040 kg) and 0.1% IPA (IPA group, 10.80 ± 0.062 kg) for 50 d. The results showed that IPA increased the proportion of glycolytic myofibers significantly in muscle ( P = 0.002). Supplementation with IPA increased PK activity ( P = 0.025) and gene expression of myosin heavy chain 4 ( MYH4 ) in muscle ( P < 0.001), and decreased the gene expression of MYH7 and MYH2 ( P < 0.01) and mitochondrial respiratory chain complexes ( P < 0.01). Supplementation with IPA enhanced insulin sensitivity and activated PI3K-Akt-mTOR pathway in vivo and accelerated differentiation of C2C12 cells in vitro. In addition, IPA affected gut microbiota by increasing the Firmicutes-to-Bacteroidetes ratio and significantly reduced the concentration of kynurenine and melatonin ( P < 0.05). In conclusion, IPA increased glycolytic myofibers and promoted muscle growth by regulating the homeostasis of glucose metabolism mediated by PI3K-mTOR signaling and the gut microbiota in piglets.