Low Protein Diets Supplemented With Alpha-Ketoglutarate Enhance the Growth Performance, Immune Response, and Intestinal Health in Common Carp (Cyprinus carpio)

Abstract

To investigate the effects of alpha-ketoglutarate (AKG) supplementation in a low protein (LP) diet on the growth performance, immune response, and intestinal health of common carp (Cyprinus carpio), 600 carp were randomly divided into five dietary groups: a normal protein (NP) diet containing 32% crude protein, an LP diet formulated with 28% crude protein, and LP with AKG at 0.4%, 0.8%, and 1.2% (dry matter). After an 8-week trial period, the results demonstrated that an LP diet led to a decrease in performance, immune response, and intestinal barrier function. Compared with the LP group, the final body weight and weight gain rate in the LP+0.4% AKG group were significantly higher, the feed conversion ratio was significantly decreased with the addition of 0.4% and 0.8% AKG. The supplementation with 0.4% and 0.8% AKG markedly increased the activities of T-SOD and GSH-Px, as well as the expression levels of GPX1a and GPX1b relative to the LP group, whereas the MDA content was significantly decreased in the LP+0.4% AKG group. In addition, the expression levels of tight junctions including claudin-3, claudin-7, ZO-1, and MLCK were significantly up-regulated in the LP+0.4% AKG group, and the relative expression levels of the pro-inflammatory factors IL-1β and IL-6α were significantly lower with the addition of 0.4%, 0.8%, and 1.2% AKG. Moreover, the abundance of Proteobacteria in the LP+0.4% AKG group was lower than that in the LP group, and the abundance of Firmicutes and Fusobacteria was higher at the phylum level. The abundance of Citrobacter in the LP+0.4% AKG group was decreased compared to the LP group, while the abundance of Aeromonas was increased at the genus level. In short, the effects of AKG on the intestinal health of the common carp were systematically and comprehensively evaluated from the perspectives of intestinal physical barrier, chemical barrier, biological barrier, and immune barrier. We found that an LP diet supplemented with 0.4% AKG was beneficial to the growth performance and intestinal health of common carp.

Histidine Deficiency Inhibits Intestinal Antioxidant Capacity and Induces Intestinal Endoplasmic-Reticulum Stress, Inflammatory Response, Apoptosis, and Necroptosis in Largemouth Bass (Micropterus salmoides)

“…Lemire et al [ 36 ] reported that glutamate, a product of histidine catabolism, was involved in the generation of the antioxidant α-ketoglutarate, which is also considered a crucial molecule in cellular redox regulation [ 36 , 37 , 38 , 39 , 40 ]. In aquatic animals, α-ketoglutarate supplementation in the diet enhanced the antioxidant capacity in grass carp [ 41 , 42 ], hybrid sturgeon ( Acipenser schrenckii ♀× A. baerii ♂ ) [ 43 ], Songpu mirror carp [ 44 ], and common carp [ 45 ]. Hence, histidine exerts its antioxidant functions through its metabolite α-ketoglutaric acid.…”

α-Ketoglutarate for Preventing and Managing Intestinal Epithelial Dysfunction

“…Alterations to villus height and cytokine profile were mitigated by the addition of 1.0% AKG to the diet [ 69 ]. Carp fed low-protein diets supplemented with 0.4% AKG exhibited reduced concentrations of IL-1b and IL-6α compared to carp on low-protein diets without AKG supplementation [ 70 ]. The addition of AKG to a low protein feed improved the growth parameters and body length [ 70 ].…”

“…AKG demonstrates the ability to alleviate oxidative stress in different animal models, leading to the restoration of vital antioxidant enzymes ( Table 1 ) [ 65 , 67 , 70 , 92 , 94 ]. For instance, in a mouse model of C. rodentium -induced colitis, the provision of 0.5% AKG in drinking water reduced serum concentrations of malondialdehyde and hydrogen peroxide [ 67 ].…”

“…In carp, a low-protein diet reduced antioxidant capabilities, including total superoxide dismutase, catalase, and glutathione peroxidase. The addition of 0.4% AKG restored antioxidant enzyme content and increased intestinal N rf 2 mRNA amounts [ 70 ]. In vitro studies have also shown that AKG normalizes antioxidant activity and reduces ROS production in intestinal porcine epithelial cells exposed to hydrogen peroxide [ 92 , 95 ].…”

“… Increased colon GSS and Nqo1 [ 65 ] Mice challenged with C. rodentium 0.5% in drinking water Decreased serum MDA and H 2 O 2 . Increased colon GSS , Nrf2 , and Nqo1 [ 67 ] Piglets challenged with LPS 1.0% in diet Increased liver GSH-Px [ 94 ] Carp on a low-protein diet 0.4, 0.8, or 1.2% in diet Increased intestinal SOD and GSH-Px [ 70 ] Abbreviations: AKG, α-ketoglutarate; C. rodentium, Citrobacter rodentium; CAT, catalase; DSS, dextran sodium sulfate; GSH, glutathione; GSH-Px, glutathione peroxidase; GSS, glutathione synthetase; H 2 O 2 , hydrogen peroxide; MDA, malondialdehyde; Nqo1, NAD(P)H Quinone dehydrogenase 1; Nrf2 , nuclear factor (erythroid-derived 2)-like 2; SOD, superoxide dismutase; T-AOC, total antioxidant capacity. …”