Metabolic flux analysis of Branched-chain amino and keto acids (BCAA, BCKA) and β-Hydroxy β-methylbutyric acid (HMB) across multiple organs in the pig.

Objective: Branched-chain amino acids (BCAA) and their metabolites the branched-chain keto acids (BCKA) and β-Hydroxy β-methylbutyric acid (HMB) are involved in the regulation of key signaling pathways in the anabolic response to a meal. However, their (inter)organ kinetics remain unclear. Therefore, BCAA (leucine (LEU), valine (VAL), isoleucine (ILE)), BCKA (α-ketoisocaproic acid (KIC), 3-methyl-2-oxovaleric acid (KMV), 2-oxoisovalerate (KIV)) and HMB across organ net fluxes were measured. Methods: In multi-catheterized pigs (n=12, ±25 kg), net fluxes across liver, portal drained viscera (PDV), kidney and hindquarter (HQ, muscle compartment) were measured before and 4h after bolus feeding of a complete meal (30% daily intake) in conscious state. Arterial and venous plasma were collected and concentrations were measured by LC- or GC-MS/MS. Data are expressed as mean[95%CI] and significance (p<0.05) from zero by Wilcoxon Signed Rank Test. Results: In the postabsorptive state (in nmol/kg bw/min), the kidney takes up HMB (3.2[1.3,5.0] ). BCKA is taken up by PDV (144[13,216]) but no release by other organs. In the postprandial state, the total net fluxes over 4h (in µmol/kg bw/4h) showed a release of all BCKA by HQ (46.2[34.2,58.2]), KIC by the PDV(12.3[7.0,17.6]) and KIV by the kidney(10.0[2.3,178]). HMB was released by the liver (0.76[0.49,1.0]). All BCKA were taken up by the liver (200[133,268]). Conclusions: Substantial differences are present in (inter)organ metabolism and transport among the BCAA and its metabolites BCKA and HMB. The presented data in a translation animal model are relevant for the future development of optimized clinical nutrition.