The contribution of the large intestine to blood acetate in man

Abstract

1. To test the hypothesis that the colon contributes significantly to venous plasma acetate concentrations, experiments were carried out in healthy volunteers and ileostomy patients. 2. Fasting plasma acetate levels were measured in 10 ileostomy patients and compared with those in 21 control subjects. Values in ileostomy patients (21.3 +/- 0.8 mumol/l) were significantly lower than in control subjects (48.0 +/- 4.2 mumol/l). 3. Plasma acetate concentration was estimated in eight healthy volunteers during 108 h of continuous fasting. Acetate concentrations rose significantly from 12 h (43.9 +/- 4.4 mumol/l) to 108 h of starvation (114.0 +/- 15.6 mumol/l) and fell back to normal fasting values on refeeding and another 12 h fast (44.3 +/- 4.7 mumol/l). 4. When colonic fermentation was stimulated after oral ingestion of 10 g of lactulose, the plasma acetate concentration increased significantly (from 44.0 +/- 7.4 to 114.4 +/- 16.2 mumol/l) in seven healthy control subjects. This rise was not affected by concomitant dosage of metronidazole. 5. These data suggest that there are at least two major sources of acetate in man, an endogenous source and the colon which probably becomes more important when fermentation of carbohydrate is occurring.

Metabolic cross talk between the colon and the periphery: implications for insulin sensitivity

“…It is well established that the colon is an important exogenous source of plasma acetate; plasma levels in subjects who have undergone ileostomy are 50 % lower than those of controls (Scheppach et al 1991). Thus, the first potential mechanism is simply that lipolysis is increased after TC because of lower circulating levels of acetate.…”

“…There are several lines of evidence that suggest a direct link between TC and changes in intermediary metabolism: (1) lower levels of systemic SCFA (Scheppach et al 1991) produced from colonic fermentation may modulate AT lipolysis (Crouse et al 1968); (2) lower levels of GLP-1 released from the distal gut may also act directly to regulate clearance of TAG-rich lipoproteins (Beck, 1989); (3) there may be a direct or indirect relationship with secondary hyperaldosteronism or the resultant hypokalaemia (Catena et al 2006).…”

Metabolic tinkering by the gut microbiome

“…58 Consistently, acetate appears to be the most abundant of these metabolites in the peripheral circulation followed by propionate and then butyrate. 57,[59][60][61] In humans, dietary manipulations designed to enhance colonic SCFA production lead to increases in serum acetate, propionate, and butyrate concentrations. 62,63 These changes can persist for hours as was demonstrated in men who ate a fiber rich evening meal and exhibited morning serum butyrate levels comparatively higher compared with those who ate a meal relatively low in fiber.…”

“…Serum acetate (~50-1000 µM) and propionate (~5-150 µM) concentrations capable of GPR43 and GPR41 activation respectively, have been observed during fasting and dietary fiber manipulation. [60][61][62][63]87,89 Serum butyrate concentrations observed after dietary fiber manipulation (1-5 µM) 62 however, are unlikely to cause significant activation of GPR109a in peripheral organs. 90 In peripheral tissue, GPR109a is activated by the ketone (D)-3-hydroxybutyrate which can reach as high as 6-8 mM during prolonged fasting.…”

Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases

“…After ethanol consumption, acetate levels are elevated by as much as 20-fold (33). Under conditions of prolonged starvation and diabetes, endogenous pathways are the main source of serum acetate (34,35). Acetate metabolism is impaired in diabetics (ref.…”