A Mixture of Valine and Isoleucine Restores the Growth of Protein-Restricted Pigs Likely through Improved Gut Development, Hepatic IGF-1 Pathway, and Plasma Metabolomic Profile

Abstract

Valine (Val) alone or in combination with isoleucine (Ile) improves the growth under severe protein restriction; however, the underlying mechanisms remain unknown. In this study, we assessed whether Val/Ile-induced growth in protein-restricted pigs is associated with changes in gut development, hepatic insulin-like growth factor 1 (IGF-1) production, and blood metabolomics. Forty piglets were assigned to five dietary groups: positive control (PC) with standard protein content; low protein (LP) with very low protein content; and LP supplemented with Val (LPV), Ile (LPI), and Val and Ile (LPVI). LPVI reversed the negative effects of VLP diets on growth and gut morphology. Both LPV and LPVI restored the reduced transcript of IGF-1 while decreasing the transcript of insulin-like growth factor binding protein 1 (IGFBP1) in the liver. LPV and LPVI recovered the reduced plasma Val, glycine, and leucine concentrations, which were positively correlated with improved gut morphology and the hepatic IGF-1 gene expression and negatively correlated with hepatic IGFBP1 mRNA abundance. In conclusion, supplementation with a combination of Val and Ile into the VLP diets restored the decreased growth performance of pigs fed with these diets likely through improved gut development, hepatic IGF-1 expression and bioavailability, and plasma metabolomics profile.

Effect of Isoleucine and Added Valine on Performance, Nutrients Digestibility and Gut Microbiota Composition of Pigs Fed with Very Low Protein Diets

“…Very low protein diets reduce the total N excretion [ 8 , 9 , 10 ], but they have an adverse effect on growth performance of pigs even when supplemented with FFL [ 11 , 12 , 13 , 14 ]. We and others have shown that supplementing BCAA, Val and a combination of Val and Ile at NRC levels partially improve the growth performance of pigs fed with VLP diets [ 16 , 18 , 24 , 28 , 29 , 30 , 31 , 32 , 33 ]. Little is understood whether a combination of Val above NRC levels and standard amount of Ile will have additive effects on growth of pigs offered VLP diets.…”

“…We and others have previously shown that supplementation of VLP or SLP diets with BCAA or Val increased the transcript of orexigenic neuropeptide Y and agouti-related protein and decreased the anorexigenic proopiomelanocortin, melanocortin-4-receptor, and cocaine- and amphetamine regulated transcript in hypothalamus, which may contribute to improved FI in BCAA supplemented groups [ 17 , 26 , 38 , 39 ]. We recently showed that Val and Ile combination added at NRC [ 15 ] levels into VLP diets improved the growth performance to the levels seen in pigs received standard protein diet [ 24 ]. The partial, but not complete recovery in growth performance in VA and VAIL groups in this study might be due to AA imbalances resulted from higher ratio of Val:Ile or ratio of Val to other AA.…”

“…We recently showed that supplementing a combination of Val and Ile at NRC [ 15 ] levels to VLP diets containing FFL improved growth performance of nursery pigs [ 24 ]. Others showed that dietary Val, and/or a combination of Val and Ile at NRC levels improved FI, growth performance and/or feed efficiency of pigs when added to both SLP [ 2 , 25 , 26 , 27 ] and VLP [ 18 , 28 , 29 , 30 , 31 , 32 , 33 ] diets containing FFL.…”

“…Dietary BCAA enhance growth likely by improving intestinal development [ 24 , 34 , 35 , 36 ], FI [ 17 , 26 , 37 , 38 , 39 ], nutrients digestibility [ 40 , 41 ], AA utilization [ 42 ], insulin-like growth factor 1 (IGF-1) signaling [ 17 ], microbiota composition [ 16 , 43 ] and muscle protein synthesis [ 26 , 44 , 45 , 46 ]. The underlying mechanisms by which dietary Val, Ile and/or combination of both improve growth performance in pigs fed with VLP diets is poorly understood.…”

Blood metabolic and physiological profiles of Bama miniature pigs at different growth stages

“…Metabolomics has widely been used since the advent of next-generation sequencing technology in pig research. It has been used to identify differences in boar sperm freezability [ 22 ], to identify the complex molecular regulatory network of meat quality in Enshi black pigs [ 23 ] and the growth mechanism of protein-restricted pigs [ 24 ].Thus, the metabolomics is suitable for our study to identify the serum difference between 6 to 12 M Bama miniature pigs.…”