Effects of the α-ketoglutaric acid on the performance, hair follicle development and antioxidant capacity of Rex rabbits

The aim of this study was to investigate the effects of α-ketoglutaric acid (AKG) supplementation on hair follicle development and to evaluate the effects on performance and antioxidant capacity in Rex rabbits. The mechanism was explored in an in vitro model and validated in an animal trial. Firstly, dermal papilla cells (DPCs) line was cultured with AKG as an in vitro model. Next, a total of 160 Rex rabbits (120-d-old, body weight 2473.20 ± 17.08 g) were divided into 4 groups with 40 rabbits in each group (20 male and 20 female) and fed with 0, 0.5%, 1.0% and 1.5% AKG diets for 35 d. The result showed that 6 mmol/L AKG significantly promoted cell proliferation (<i>P <</i> 0.001), reduced the proportion of cells in the synthesis (S) phase and increased the gap 2 (G2) phase (<i>P <</i> 0.01). Transcriptomics results indicated that AKG enhanced DPCs exosome secretion capacity, increased susceptibility to extracellular signaling molecules, and improved their regulatory effects on neighboring cells. Additionally, the findings suggested that AKG-mediated promotion of hair follicle development may be associated with wingless/integrated (Wnt) signaling pathway. Meanwhile, AKG enhanced the expression levels of genes and proteins in the Wnt signaling pathway in DPCs and Rex rabbit skin tissue (<i>P</i> < 0.05). AKG treatment increased the concentrations of glutamine, glutamic acid, asparagine and aspartic acid amino acids in the DPCs (<i>P <</i> 0.05). Finally, 1.5% AKG significantly increased the performance, slaughter performance, primary hair follicle density, secondary hair follicle density and total hair follicle density of Rex rabbits, significantly increasing the antioxidant capacity in the skin, liver and serum of Rex rabbits, while up-regulating the expression of anti-apoptotic and antioxidant-related genes in skin tissues (<i>P <</i> 0.05). In summary, dietary supplementation of 1.5% AKG significantly improved performance, hair follicle density and antioxidant capacity in Rex rabbits. AKG may promote hair follicle development by reducing intracellular amino acid catabolism and enhancing the Wnt signaling pathway.