title: Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids.
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-(13)C]acetate, [2-(13)C]propionate, or [2,4-(13)C2]butyrate directly in 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 eightfold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6-h infusion period. Altogether, gut-derived acetate, propionate, and butyrate play important roles as substrates for glucose, cholesterol, and lipid metabolism.
authors.affiliation: Hanzeplein 1, 9713 GZ Groningen, The Netherlands. D.J.Reijngoud01@umcg.nl.
authors.forename: Gijs
authors.initials: G
authors.lastname: den Besten
authors.forename: Katja
authors.initials: K
authors.lastname: Lange
authors.forename: Rick
authors.initials: R
authors.lastname: Havinga
authors.forename: Theo H
authors.initials: TH
authors.lastname: van Dijk
authors.forename: Albert
authors.initials: A
authors.lastname: Gerding
authors.forename: Karen
authors.initials: K
authors.lastname: van Eunen
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Hooiveld
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bakker
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Reijngoud
mesh_terms: D000818:Animals; D002432:Cecum / Q000378:metabolism / Q000382:microbiology; D002784:Cholesterol / Q000096:biosynthesis; D005232:Fatty Acids, Volatile / Q000008:administration & dosage / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000502:physiology; D023421:Models, Animal; D010168:Palmitates / Q000378:metabolism; D011422:Propionates / Q000378:metabolism
chemical_list: D005232:Fatty Acids, Volatile; D010168:Palmitates; D011422:Propionates; D002784:Cholesterol; D005947:Glucose
keywords: glucose metabolism; gut-microbial metabolism; lipid metabolism; metabolic regulation