Transorgan Short-Chain Fatty Acid Fluxes in the Fasted and Postprandial State in the Pig

Author(s):  
Sarah K Kirschner ◽  
Gabriella A.M. Ten Have ◽  
Marielle P.K.J. Engelen ◽  
Nicolaas E.P. Deutz

The short-chain fatty acids (SCFAs) acetate, propionate, butyrate, isovalerate, and valerate are end products of intestinal bacterial fermentation and important mediators in the interplay between the intestine and peripheral organs. To unravel the transorgan fluxes and mass balance comparisons of SCFAs, we measured their net fluxes across several organs in a translational pig model. In multi-catheterized conscious pigs (n=12, 25.6 (95% CI [24.2, 26.9]) kg, 8-12 weeks old), SCFA fluxes across portal drained viscera (PDV), liver, kidneys, and hindquarter (muscle compartment) were measured after an overnight fast and in the postprandial state, 4 h after administration of a fiber-free, mixed meal. PDV was the main releasing compartment of acetate, propionate, butyrate, isovalerate, and valerate during fasting and in the postprandial state (all P=0.001). Splanchnic acetate release was high due to the absence of hepatic clearance. All other SCFAs were extensively taken up by the liver (all P<0.05). Even though only 7% [4, 10] (propionate), 42% [23, 60] (butyrate), 26% [12, 39] (isovalerate), and 3% [0.4, 5] (valerate) of PDV release were excreted from the splanchnic area in the fasted state, splanchnic release of all SCFAs was significant (all P≤0.01). Splanchnic propionate, butyrate, isovalerate and valerate release remained low but significant in the postprandial state (all P<0.01). We identified muscle and kidneys as main peripheral SCFA metabolizing organs, taking up the majority of all splanchnically released SCFAs in the fasted state and in the postprandial state. We conclude that the PDV is the main SCFA releasing and the liver the main SCFA metabolizing organ. Splanchnically released SCFAs appear to be important energy substrates to peripheral organs not only in the fasted but also in the postprandial state.

2000 ◽  
Vol 83 (5) ◽  
pp. 521-531 ◽  
Author(s):  
Pierre Nozière ◽  
Cécile Martin ◽  
Didier Rémond ◽  
Niels B. Kristensen ◽  
Richard Bernard ◽  
...  

Four ewes, each fitted with a rumen cannula and with catheters in the mesenteric artery and portal and mesenteric veins, received continuous intrarumen infusions of water or of short-chain fatty acids (SCFA). SCFA infusions were isoenergetic (83 kJ/h) and provided rumen molar proportions (acetate : propionate : butyrate) of 70 : 20 : 10, 50 : 40 : 10 or 50 : 20 : 30. The rumen SCFA production rate with the basal diet was 90·0, 23·1 and 8·8 mmol/h for acetate, propionate and butyrate respectively. Portal net fluxes indicated that 74, 67 and 22–30 % of infused acetate, propionate and butyrate respectively, reached the portal vein. Portal net release of β-hydroxybutyrate increased with SCFA infusions, irrespective of the amount of butyrate infused. Portal net release of lactate decreased with high-butyrate infusion. Portal net uptake of glucose increased with the SCFA infusions. In ewes infused with water, a portal net uptake of total amino acids (AA) was observed. SCFA infusions decreased the uptake of nonessential AA (glutamate, glycine, but not glutamine) and increased the net release of tyrosine and essential AA (isoleucine, leucine). Portal net fluxes of AA were similar with both high-acetate and high-propionate infusions. Lower net uptake of glutamine and net release of most essential AA and some nonessential AA were observed with the high-butyrate infusion. Energetic summation of portal net release was not significantly different between the three SCFA infusions, although it tended to be lower with high-butyrate infusion. This may be related to the higher trophic effect of butyrate on the digestive mucosa.


2005 ◽  
Vol 33 (1) ◽  
pp. 237-240 ◽  
Author(s):  
V. Ganapathy ◽  
E. Gopal ◽  
S. Miyauchi ◽  
P.D. Prasad

SLC5A8 is a candidate tumour suppressor gene that is silenced in colon cancer, gastric cancer and possibly other cancers in humans. This gene codes for a transporter belonging to the Na+/glucose co-transporter gene family (SLC5). The cancer-associated silencing of the gene involves hypermethylation of CpG islands present in exon 1 of the gene. SLC5A8 is expressed in colon, ileum, kidney and thyroid gland. The protein coded by the gene mediates the Na+-coupled and electrogenic transport of a variety of monocarboxylates, including short-chain fatty acids, lactate and nicotinate. It may also transport iodide. The normal physiological function of this transporter in the intestinal tract and kidney is likely to facilitate the active absorption of short-chain fatty acids, lactate and nicotinate. One of the short-chain fatty acids that serves as a substrate for SLC5A8 is butyrate. This fatty acid is an inhibitor of histone deacetylases and is known to induce apoptosis in a variety of tumours including colonic tumour. Since butyrate is produced in the colonic lumen at high concentrations by bacterial fermentation of dietary fibre, we speculate that the ability of SLC5A8 to mediate the entry of this short-chain fatty acid into colonic epithelial cells underlies the potential tumour suppressor function of this transporter.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 436
Author(s):  
Cheng Li ◽  
Zhiqian Liu ◽  
Carolyn Bath ◽  
Leah Marett ◽  
Jennie Pryce ◽  
...  

Short-chain fatty acids (SCFA, C2-C5) in milk and serum are derived from rumen bacterial fermentation and, thus, have the potential to be used as biomarkers for the health status of dairy cows. Currently, there is no comprehensive and validated method that can be used to analyse all SCFAs in both bovine serum and milk. This paper reports an optimised protocol, combining 3-nitrophenylhydrazine (3-NPH) derivatisation and liquid chromatography-mass spectrometry (LC-MS) analysis for quantification of SCFA and β-hydroxybutyric acid (BHBA) in both bovine milk and bovine serum. This method is sensitive (limit of detection (LOD) ≤ 0.1 µmol/L of bovine milk and serum), accurate (recovery 84–115% for most analytes) and reproducible (relative standard deviation (RSD) for repeated analyses below 7% for most measurements) with a short sample preparation step. The application of this method to samples collected from a small cohort of animals allowed us to reveal a large variation in SCFA concentration between serum and milk and across different animals as well as the strong correlation of some SCFAs between milk and serum samples.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
Fabrizio Montecucco ◽  
Giorgio Luciano Viviani

In type 2 diabetes, hyperglycemia, insulin resistance, increased inflammation, and oxidative stress were shown to be associated with the progressive deterioration of beta-cell function and mass. Short-chain fatty acids (SCFAs) are organic fatty acids produced in the distal gut by bacterial fermentation of macrofibrous material that might improve type 2 diabetes features. Their main beneficial activities were identified in the decrease of serum levels of glucose, insulin resistance as well as inflammation, and increase in protective Glucagon-like peptide-1 (GLP-1) secretion. In this review, we updated evidence on the effects of SCFAs potentially improving metabolic control in type 2 diabetes.


2006 ◽  
Vol 76 (2) ◽  
pp. 57-64 ◽  
Author(s):  
Hsien-Tsung Yao ◽  
Meng-Tsan Chiang

Chitosan has been shown to have lipid-lowering effects, but little is known about the effect of chitosan on colonic pH value and short-chain fatty acid (SFCA) concentration. This study was designed to investigate the effect of chitosan on colonic bacterial fermentation and fecal bacterial enzyme activity in rats fed a diet enriched in cholesterol. Male Sprague-Dawley rats were fed a diet containing 5% cellulose (CE) or 5% chitosan (CS) for 15 days. Significantly increased fecal cholesterol and triacylglycerols contents were observed in rats fed the chitosan diet. In addition, lower cecal acetate and butyrate concentrations and higher fecal acetate, propionate, and butyrate concentrations were observed in rats fed the CS diet when compared to those fed the CE diet. Although rats fed with the CS diet exhibited an elevated cecal (cecum with contents) weight and higher pH value, no significant difference in fecal pH value was observed between the CE group and the CS group. Chitosan significantly decreased fecal mucinase and beta-glucuronidase activities. Results from this study show that chitosan may alter fecal bacterial enzyme activities and SCFA concentrations and the beneficial effects of chitosan on the colonic environment may occur in the distal colon in rats.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hidenori Shimizu ◽  
Yuki Masujima ◽  
Chihiro Ushiroda ◽  
Rina Mizushima ◽  
Satsuki Taira ◽  
...  

Abstract Fermented foods represent a significant portion of human diets with several beneficial effects. Foods produced by bacterial fermentation are enriched in short-chain fatty acids (SCFAs), which are functional products of dietary fibers via gut microbial fermentation. In addition to energy sources, SCFAs also act as signaling molecules via G-protein coupled receptors such as FFAR2 and FFAR3. Hence, dietary SCFAs in fermented foods may have a direct influence on metabolic functions. However, the detailed mechanism by dietary SCFAs remains unclear. Here, we show that dietary SCFAs protected against high-fat diet-induced obesity in mice in parallel with increased plasma SCFAs without changing cecal SCFA or gut microbial composition. Dietary SCFAs suppressed hepatic weight and lipid synthesis. These effects were abolished in FFAR3-deficient mice but not FFAR2-deficient. Thus, SCFAs supplementation improved hepatic metabolic functions via FFAR3 without influencing intestinal environment. These findings could help to promote the development of functional foods using SCFAs.


1994 ◽  
Vol 266 (3) ◽  
pp. R889-R895 ◽  
Author(s):  
T. R. Strack ◽  
P. Poussier ◽  
E. B. Marliss ◽  
A. M. Albisser

Because the dog can respond to a mixed-meal challenge with little or no change in plasma glucose concentration, we used kinetic techniques to quantify the magnitude and duration of changes in glucoregulation. Glucose turnover was measured using [3-3H]glucose and [U-14C]glucose over two 19-h periods in healthy dogs, first during a fast (n = 6) and then throughout the postprandial state (n = 6) after a single mixed meal. Mean arterial glycemia remained constant in the fasted state (7.5 +/- 0.2 mM) and in the fed state (7.6 +/- 0.3 mM). Glucose appearance (Ra), however, increased slowly after the meal from 38 +/- 2 mg/min to a maximum of 79 +/- 8 mg/min after 6 h and stayed elevated until 12 h (P < 0.001). In parallel, glucose disappearance (Rd) rose from 35 +/- 3 to 83 +/- 7 mg/min, closely matching the corresponding Ra. Glucose recycling rose from 25 +/- 8% at baseline to a maximum of 53 +/- 15% (P < 0.05) at 14 h in fed dogs, whereas levels for fasted dogs stayed between 19 +/- 7% at 0 h and 27 +/- 12% at 6 h. Insulin levels rose significantly 30 min after the meal from 67 +/- 7 pM to a peak of 208 +/- 54 pM at 6 h but remained elevated for 12 h. We conclude that 1) the dog was able to maintain postprandial glucoregulation by very precise matching of Ra and Rd such as to maintain glycemia constant.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 12 ◽  
Author(s):  
María Daniella Carretta ◽  
John Quiroga ◽  
Rodrigo López ◽  
María Angélica Hidalgo ◽  
Rafael Agustín Burgos

Short-chain fatty acids (SCFAs) are the main metabolites produced by the bacterial fermentation of dietary fiber, and they play a critical role in the maintenance of intestinal health. SCFAs are also essential for modulating different processes, and they have anti-inflammatory properties and immunomodulatory effects. As the inflammatory process predisposes the development of cancer and promotes all stages of tumorigenesis, an antitumor effect has also been associated with SCFAs. This is strongly supported by epidemiological studies showing that a diet rich in fiber is linked to a reduced risk of colon cancer and has significant clinical benefits in patients with inflammatory bowel disease (IBD). SCFAs may signal through the metabolite-sensing G protein-coupled receptors free fatty acid receptor 3 [FFAR3 or G protein-coupled receptor 41 (GPR41)], FFAR2 (GPR43), and GPR109A (also known as hydroxycarboxylic acid receptor 2 or HCAR2) expressed in the gut epithelium and immune cells. This review summarizes the existing knowledge regarding the SCFA-mediated suppression of inflammation and carcinogenesis in IBD and colon cancer.


2015 ◽  
Vol 309 (3) ◽  
pp. E256-E264 ◽  
Author(s):  
Marieke G. Schooneman ◽  
Gabriella A. M. Ten Have ◽  
Naomi van Vlies ◽  
Sander M. Houten ◽  
Nicolaas E. P. Deutz ◽  
...  

Acylcarnitines are derived from mitochondrial acyl-CoA metabolism and have been associated with diet-induced insulin resistance. However, plasma acylcarnitine profiles have been shown to poorly reflect whole body acylcarnitine metabolism. We aimed to clarify the individual role of different organ compartments in whole body acylcarnitine metabolism in a fasted and postprandial state in a porcine transorgan arteriovenous model. Twelve cross-bred pigs underwent surgery where intravascular catheters were positioned before and after the liver, gut, hindquarter muscle compartment, and kidney. Before and after a mixed meal, we measured acylcarnitine profiles at several time points and calculated net transorgan acylcarnitine fluxes. Fasting plasma acylcarnitine concentrations correlated with net hepatic transorgan fluxes of free and C2- and C16-carnitine. Transorgan acylcarnitine fluxes were small, except for a pronounced net hepatic C2-carnitine production. The peak of the postprandial acylcarnitine fluxes was between 60 and 90 min. Acylcarnitine production or release was seen in the gut and liver and consisted mostly of C2-carnitine. Acylcarnitines were extracted by the kidney. No significant net muscle acylcarnitine flux was observed. We conclude that liver has a key role in acylcarnitine metabolism, with high net fluxes of C2-carnitine both in the fasted and fed state, whereas the contribution of skeletal muscle is minor. These results further clarify the role of different organ compartments in the metabolism of different acylcarnitine species.


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