Time of day and glucose tolerance status affect serum short-chain fatty concentrations in humans

Abstract

Short-chain fatty acids (SCFA) are derived from endogenous (metabolism of fat, carbohydrate, and amino acids) and exogenous (colonic fermentation) sources. To see how time of day and glucose tolerance status influenced serum SCFA concentrations, we determined serum SCFA throughout the day in 22 subjects with impaired glucose tolerance (IGT) and 10 young and eight middle-aged normal controls. On 1 day, insulin sensitivity was assessed as the steady-state plasma glucose (SSPG) level achieved during intravenous infusion of glucose insulin, and somatostatin. On another day, plasma glucose and insulin and serum SCFA levels were measured 12 times over 12 hours subjects eating a standard diet. SSPG in young onctrols (5.5 ± 1.1 mmol/L) was less than in middle-aged controls (9.3 ± 1.6 mmol/L), which in turn was less than in IGT subjects (13.7 ± 0.6 mmol/L; P < .01). Mean plasma glucose in IGT subjects was greater than in normal controls, and mean plasma insulin in IGT subjects was higher than in young controls but similar to the levels in middle-aged controls. Mean 12-hour serum acetate in young controls (143 ± 13 μmol/L) was greater than in middle-aged controls (104 ± 11 μmol/L) and IGT subjects (113 ± 5 μmol/L; P < .05). Mean 12-hour serum propionate in young controls (3.8 ± 0.5 μmol/L) was less than in IGT subjects (5.4 ± 0.3 μmol/L; P < .01), with middle-aged controls being intermediate (4.6 ± 0.3 μmol/L). Both young (1.6 ± 0.3 μmol/L) and middle-aged (1.0 ± 0.2) controls had lower mean butyrate than IGT subjects (3.1 ± 0.4 μmol/L; P < .05). Levels of all three SCFA varied significantly during the day, tending to decrease after breakfast and increase transiently after lunch and dinner. It is concluded that both time of day and glucose tolerance status affect serum SCFA levels in nondiabetic humans. The results suggest that serum acetate is derived primarily from colonic fermentation, serum butyrate primarily from endogenous fatty acid metabolism, and serum propionate from both exogenous and endogenous sources.