Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids

G. den Besten, K. Lange, R. Havinga, T.H. van Dijk, A. Gerding, K. van Eunen, M.R. Müller, A.K. Groen, G.J.E.J. Hooiveld, B.M. Bakker, D.J. Reijngoud

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244 Citations (Scopus)

Abstract

Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism.
Original languageEnglish
JournalAmerican Journal of Physiology. Gastrointestinal and Liver Physiology
Volume305
Issue numberG900-G910
DOIs
Publication statusPublished - 2013

Keywords

  • isolated rat hepatocytes
  • hepatic glucose-production
  • distal ulcerative-colitis
  • insulin-resistance
  • butyrate formation
  • epithelial-cells
  • human colon
  • metabolism
  • mice
  • acetate

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