Quantitative Differences in Interorgan Kinetics of Short-Chain Fatty Acids (SCFA)

Abstract

Abstract Objectives The short-chain fatty acids (SCFA) acetate (C2), propionate (C3), butyrate (C4), isovalerate (Ci5), and valerate (C5) are endproducts of anaerobic fermentation by the intestinal microbiota and known to play a crucial role as energy source for colonocytes (C2 and C4) and muscle (C2), and as mediators in signaling pathways. To unravel the interorgan kinetics of SCFA, we measured their net balances across organs in a translational pig model. Methods In multi-catheterized conscious pigs (n = 11, 25.6 ± 2.2 kg), net balances across portal drained viscera (PDV), liver, kidney and hindquarter (HQ, muscle compartment) were measured in the postabsorptive state. Arterial and venous plasma (in μM) was collected and concentrations were measured by GC-MS. Data are mean (SE). Net balance in nmol/kg BW/min. Significance (P < 0.05) from zero was tested by Wilcoxon Signed Rank Test. Results In the postabsorptive state, arterial concentrations were C2: 189.1 (17.1), C3: 4.8 (0.3), C4: 7.1 (0.9), Ci5: 0.45 (0.09) and C5: 0.15 (0.03). A net release of C2 by PDV (8764 (527.5)) and liver resulted in a high splanchnic release (10,969 (1205)). PDV release of C3 was 2893 (353.9), of C4 1081 (175.9), of Ci5 133.7 (11.1), and of C5 271.2 (44.7). In contrast to C2, after extensive hepatic uptake, splanchnic release of C3, C4, Ci5, and C5 was only 6.5 (0.5)%, 39.3 (8.3)%, 26.3 (6.0)%, and 3.7 (0.9)% of the PDV release. All SCFA were taken up by HQ and kidney. However, while only 62% of C2 released by splanchnic compartment were taken up by muscle (hindquarter and forequarter) and kidneys, net uptake of C3, C4, Ci5 and C5 by muscle and kidney was comparable to splanchnic release. Conclusions Interorgan kinetics differ between C2 and the other SCFA. Due to differences in hepatic SCFA metabolism, acetate is the main SCFA in the systemic circulation possibly acting as energy source to muscle tissue, kidneys and organs or tissues not analyzed in this study. The liver controls the systemic concentrations of all other SCFA. Funding Sources Huffines Institute for Sports Medicine and Human Performance.