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Effect of increasing ruminal butyrate absorption on splanchnic metabolism of volatile fatty acids absorbed from the washed reticulorumen of steers¹

N. B. Kristensen^*,2 and D. L. Harmon

^* Department of Animal Nutrition and Physiology, Danish Institute of Agricultural Sciences, Denmark; and and Department of Animal Sciences, University of Kentucky, Lexington 40546

	Abstract

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Four steers fitted with a ruminal cannula and chronic indwelling catheters in the mesenteric artery, mesenteric vein, hepatic portal vein, hepatic vein, and the right ruminal vein were used to study the absorption and metabolism of VFA from bicarbonate buffers incubated in the temporarily emptied and washed reticulorumen. Portal and hepatic vein blood flows were determined by infusion of p-aminohippurate into the mesenteric vein, and portal VFA fluxes were calibrated by infusion of isovalerate into the ruminal vein. The steers were subjected to four experimental treatments in a Latin square design with four periods within 1 d. The treatments were Control (bicarbonate buffer) and VFA buffers containing 4, 12, or 36 mmol butyrate/kg of buffer, respectively. The acetate content of the buffers was decreased with increasing butyrate to balance the acidity. The butyrate absorption from the rumen was 39, 111, and 300 ± 4 mmol/h for the three VFA buffers, respectively. The ruminal absorption rates of propionate (260 ± 12 mmol/h), isobutyrate (11.4 ± 0.7 mmol/h), and valerate (17.3 ± 0.7 mmol/h) were not affected by VFA buffers. The portal recovery of butyrate and valerate absorbed from the rumen increased (P < 0.01) with increasing butyrate absorption and reached 52 to 54 ± 4% with the greatest butyrate absorption. The liver responded to the increased butyrate absorption with a decreasing fractional extraction of propionate and butyrate, and with the greatest butyrate absorption, the splanchnic flux was 22 ± 1% and 18 ± 1% of the absorbed propionate and butyrate, respectively. The increased propionate and butyrate release to peripheral tissues was followed by increased (P < 0.05) arterial concentrations of propionate (0.08 ± 0.01 mmol/kg) and butyrate (0.07 ± 0.01 mmol/kg). Arterial insulin concentration increased (P = 0.01) with incubation of VFA buffers compared with Control and was numerically greatest with the greatest level of butyrate absorption. We conclude that the capacity to metabolize butyrate by the ruminal epithelium and liver is limited. If butyrate absorption exceeds the metabolic capacity, it affects rumen epithelial and hepatic nutrient metabolism and affects the nutrient supply of peripheral tissues.

Key Words: Butyric Acid • Cattle • Energy Metabolism • Volatile Fatty Acids

	Introduction

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Butyrate is considered to be a favored metabolite for gut epithelia (Topping and Clifton, 2001) and the high affinity of the ruminal epithelium (Pennington, 1952) and other gut epithelia toward butyrate, compared with acetate and propionate, has previously been explained by butyrate being an important energy source for epithelial cells (Bugaut, 1987). When butyrate appears in the systemic circulation or is added to cell cultures, it has a number of effects: inhibition of growth and induction of morphological changes in cultured cells of different origins (Prasad and Sinha, 1976; Gálfi et al., 1991), increased insulin secretion (Manns and Boda, 1967), inhibition of gastrointestinal motility by epithelial receptors (Crichlow, 1988) and/or systemic effects (Le Bars et al., 1954), and stimulation of rumen epithelial development (Sander et al., 1959). In addition, when butyrate is given intravenously, it is toxic (Manns and Boda, 1967). Therefore, we could speculate that the reason the gut epithelia metabolize butyrate is not only to harvest acetyl-CoA units, but also to benefit the whole organism by decreasing the butyrate load of the liver and peripheral tissues. Valerate is also efficiently metabolized by the ruminal epithelium (Kristensen et al., 2000b), and partial oxidation of butyrate, valerate, and perhaps other acids by gut epithelia could be beneficial in that their metabolism generates more polar molecules that are less permeable to random membrane passage. The current study was undertaken to study the metabolic capacity of the ruminal epithelium for butyrate and how increasing butyrate load affects splanchnic metabolism of selected nutrients.

	Materials and Methods

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All procedures involving animals were approved by the University of Kentucky Animal Care and Use Committee (Protocol No. 00387A2002).

Animals and Feeding
Four Holstein bull calves were fitted with a ruminal cannula (No. 2C ruminal cannula, Bar Diamond Inc., Parma, ID), castrated, and fitted with permanent indwelling catheters in the mesenteric artery, mesenteric vein, hepatic portal vein, and the hepatic vein (Huntington et al., 1989) as well as in the right ruminal vein (silicone tubing, 1.02 mm i.d., 2.16 mm o.d., Helix Medical Inc., Carpinteria, CA). The ruminal vein catheter was inserted 25 cm into a small branch separated by blunt dissection approximately at the middle of the abdominal surface of the rumen.

The steers were sampled 41 to 52 d after surgery at an average BW of 275 ± 6 kg. Catheter patency was maintained by weekly aspiration of catheter fluid, flushing with saline, and filling with saline containing 100 U/mL of heparin and 0.1% benzyl alcohol.

Steers were fed 3.4 kg DM/d of mixed grass hay and 3.3 kg DM/d of corn-based concentrate (composition of entire diet DM basis, %: OM, 94; crude fat, 4; CP, 13; NDF, 34) for at least 14 d before sampling. The steers had access to a mineral mix (Burkman Feeds, Danville, KY; composition of the DM: Ca, 13 to 15%; P, 6%; NaCl, 17 to 20%; Mg, 3%; S, 1%; K, 1%; Zn 2,300 ppm; Mn, 2,200 ppm; Cu, 1,050 ppm; I, 45 ppm; Co, 15 ppm; and Se, 29 ppm). The mineral mix contained vitamin A (66,000 IU/100 g) and vitamin E (28 IU/100 g). The steers were housed individually in 3 x 3 m pens at 18 to 24°C, with lighting from 0530 to 2130. Steers had free access to water except during samplings. The steers were fed once daily (between 0730 and 0830), except on sampling days, when they were fed after the experimental procedure was completed.

Intravenous Infusion
One steer was sampled per sampling day. The steers were weighed and continuous infusion of p-aminohippuric acid (pAH; 16 ± 1 mmol/h; Sigma-Aldrich Corp., St. Louis, MO) into the mesenteric vein and saline (The Butler Co., Columbus, OH) into the ruminal vein was initiated. When the second ruminal buffer incubation was initiated (see below), the ruminal vein infusion was changed from saline to isovalerate (14.9 ± 0.3 mmol/h; isovaleric acid 99%, Acros Organics, Geel, Belgium). The infusates were prepared the day before sampling by dissolving pAH (250 mmol/kg of infusate) as well as isovaleric acid (220 mmol/kg of infusate) in sterile water (The Butler Co.). The pH of the pAH and isovalerate infusates was adjusted to 7.4. The infusates were transferred to autoclaved bottles by sterile filtration (0.2-µm Nalgene sterile filter, Nalge Nunc Int., Rochester, NY). Infusion rates were determined gravimetrically, and infusion solutions were weighed multiple times during infusions to ensure that the infusion rates were constant throughout the sampling day.

Washed Rumen Procedure
After the i.v. infusions were initiated, the rumen was emptied and washed with approximately 3 x 5 L of warm tap water and 10 L of saline. The ruminal contents were stored in a plastic barrel and warmed before reintroduction to the steer at the end of the day. The steers were subjected to four treatments in a Latin square design (control, 4, 12, and 36 mM butyrate in the ruminal buffer), with four periods within a sampling day. Treatments were arranged in a Latin square so that all steers received each treatment once, and all treatments appeared once as the first, second, third, and fourth ruminal buffer treatment during the course of a sampling day. Control was a 45-min incubation of 15 kg of bicarbonate buffer without VFA and no infusion into the rumen during the incubation (Table 1). Previous studies showed that splanchnic nutrient fluxes reached a new steady state quickly after start of incubation of ruminal buffers without VFA and were stable for more than 4 h (Kristensen et al., 2000a; Kristensen and Harmon, 2004). It was therefore decided to allocate more time to the VFA buffer treatments compared with the control. The three VFA buffer treatments added increasing amounts of butyrate with the ruminal buffers and infusates. The acidity of the buffer system was balanced by decreasing the acetate concentration equivalent with the increasing butyrate concentration of ruminal buffers and infusates (Table 1). With VFA buffers, 15 kg of the respective buffer was incubated for 125 min in the rumen along with continuous intraruminal infusion of ruminal infusate (1,022 ± 9 g/h; Table 1). All buffers and saline added to the rumen were heated to 40°C overnight in a forced-air oven. An infusion and gassing device described previously (Kristensen et al., 2002), was placed in the buffer in the rumen and the ruminal cannula was closed. The buffer in the rumen was continuously gassed with a mixture of 75% CO₂ and 25% N₂. Each treatment was terminated by emptying the rumen followed by washing of the rumen with 7.5 kg of saline. After the sampling procedures were completed, the ruminal contents were warmed in a water bath, filled back into the rumen, and the steer was fed.

Ruminal buffer samples (20 mL) were obtained after a 30-, 60-, 90-, and 120-min VFA buffer incubation. Samples were also obtained from buffers and saline pumped out of the rumen after the incubations. Buffer pH was measured immediately and the buffer samples were stored and transported as described for blood plasma.

Analytical Procedures
Plasma concentrations of L-lactate (L-lactate oxidase), D-glucose (D-glucose oxidase), L-glutamate (L-glutamate oxidase), and L-glutamine (glutaminase plus L-glutamate oxidase) were determined by membrane-immobilized enzymes (Yellow Spring Instruments, OH). Membrane linearity was checked daily according to the manufacturer’s recommendations. Plasma concentrations of D-3-hydroxybutyrate were determined using a kit based on D-3-hydroxybutyrate dehydrogenase (Stanbio Laboratory, Boerne, TX). Plasma pAH concentrations were determined colorimetrically as previously described (Harvey and Brothers, 1962 [Au: Not in Lit Cited]). Volatile fatty acid concentrations in infusates, buffers, and plasma were measured as previously described (Kristensen, 2000). Plasma insulin was determined in samples pooled within treatment as described previously (Toivonen et al., 1986).

Calculations and Statistical Procedures
Data on lactate, glucose, glutamine, glutamate, and 3-hydroxybutyrate are reported as plasma concentrations and plasma fluxes. Blood flow rates and fluxes of VFA are given as whole blood values. Blood concentrations of VFA were obtained from plasma concentrations assuming a 45% dilution space for VFA in erythrocytes (Kristensen, 2000). The net portal flux_ij was calculated as follows:

using either whole blood or plasma values as indicated, i = steer 1 to 4 and j = sample 1 to 10. The net hepatic flux_ij was calculated as follows:

The hepatic extraction ratio_ij was calculated as follows:

Ruminal VFA absorption was calculated as follows:

Isovalerate corrected recovery of ruminally absorbed VFA was calculated as follows:

where i = steer 1 to 4, and j 1 to 3 = butyrate level 4, 12, and 36. The portal recovery of isovalerate was calculated from the difference in portal flux between the period with saline and isovalerate infusion into the ruminal vein. In the calculation of portal isovalerate flux, it was assumed that 50% of the arterial isovalerate was taken up by the portal-drained viscera (PDV). The following weights were assigned in calculating acetyl unit balance: acetate = 1, butyrate = 2, valerate = 1, and 3-hydroxybutyrate = 2. The following weights were assigned in calculation of propionyl unit balance: propionate = 1, isobutyrate = 1, valerate = 1, lactate = 1, and glucose = 2.

The weight difference between ruminal buffer added to the rumen and buffer pumped out after 125 min of incubation was evaluated by paired t-test within each treatment using the means procedure of SAS (SAS Inst., Inc., Cary, NC). Effects of buffer treatment on ruminal variables, recovery of isovalerate infused into the ruminal vein, and portal and splanchnic VFA recovery were analyzed as an incomplete Latin square with one missing cell in each period within day (i.e., control treatment). The model included treatment and steer. For arterial concentrations and flux data the contrast Control vs. others was used to test the overall effect of VFA absorption vs. no VFA absorption. Orthogonal contrasts were used to test for linear and quadratic effects of butyrate. No VFA was present in the control treatment, and the orthogonal contrasts did not include the control treatment. Significance was declared for P < 0.05 and a tendency for 0.05 < P < 0.10. Means in the text are means of four steers ± SEM.

	Results and Discussion

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Ruminal Variables
It was essential to the present experiment that the ruminal variables reached a steady state quickly after initiation of the individual treatments. The VFA concentrations in the ruminal buffers were found to be stable (butyrate given as example in Figure 1); however, acetate, propionate, and valerate were absorbed slightly faster than predicted, whereas isobutyrate and butyrate at the greatest infusion level were absorbed slightly slower than assumed (Table 2). The fractional absorption rate of butyrate tended (P = 0.09) to decrease with increased butyrate absorption, and the fractional absorption rate of valerate decreased (P = 0.05) with increased butyrate absorption. The ruminal pools of butyrate and valerate increased (P = 0.01; data not shown) during incubation with increasing butyrate in agreement with the treatment effects on the fractional absorption rates of butyrate and valerate. The buffer mass in the rumen increased during incubation of all buffers with VFA (1.8 ± 0.2 kg; P < 0.05; data not shown); however, no differences (P = 0.43) were found among treatments.

View larger version (15K): [in this window] [in a new window]   Figure 1. Ruminal concentration of butyrate with incubation of bicarbonate buffers in the washed rumen of steers with initial butyrate levels of 4 (•), 12 (), and 36 () mmol/kg of buffer, respectively. Each value is the mean of four steers ± SEM (partly covered by the symbols).

The effect of increased ruminal butyrate on the fractional absorption rate of butyrate (tendency) and valerate could at first seem to contradict the assumption that VFA are absorbed primarily by nonionic diffusion (Rechkemmer, 1991). However, because of the effect of the increased ruminal butyrate absorption on the epithelial metabolism (see below), both butyrate and valerate concentrations in the epithelium and serosal extracellular space seemed to increase disproportionally to the butyrate and valerate concentrations in the ruminal buffer. In the current study, the transepithelial concentration gradient for butyrate and valerate was, therefore, not linearly related to the ruminal concentration. The decreased fractional absorption rate with the greatest butyrate load is likely a reflection of the interaction between metabolism and transepithelial concentration gradient and cannot be taken as an indication for a mediated transport mechanism for VFA. In support of this conclusion, we did not observe treatment effects on the fractional absorption rates of acetate, propionate, or isobutyrate. Therefore, if the decreased fractional absorption rates of butyrate and valerate were caused by a limited capacity of a trans-membrane transport system for VFA (Kramer et al., 1996), there would need to be at least two transport systems with different substrate specificities. The fractional absorption rates of VFA were in the order isobutyrate < acetate = propionate = butyrate < valerate, which is in agreement with previous findings in sheep (Oshio and Tahata, 1984; Kristensen et al., 2000a). The results of the current study also agree with previous studies showing that the fractional absorption rates of acetate, propionate, and butyrate are similar at ruminal pH above 6.3 (Dijkstra et al., 1993; López et al., 2003).

Arterial Concentrations
The packed cell volume, as well as the arterial concentration of valerate and glucose, was not affected by incubation of VFA buffers compared with Control (Table 3). The arterial concentration of all other metabolites and insulin were altered by VFA treatment (P < 0.05) compared with Control. Arterial acetate and glucose decreased linearly (P < 0.05), whereas propionate, isobutyrate, and 3-hydroxybutyrate all increased linearly (P < 0.05) with increasing butyrate in ruminal buffers. The decreasing acetate was probably caused by the decreasing acetate concentration in the VFA buffers and not by the butyrate treatment per se. There was a quadratic increase (P < 0.05) in arterial butyrate, reflecting a disproportionate increase in arterial butyrate with the greatest level of ruminal butyrate. The high arterial concentrations of propionate and butyrate with the greatest ruminal absorption of butyrate correlates with an increased splanchnic recovery of these metabolites (see below) and indicate that peripheral tissues were exposed to a substantial increased supply of these VFA. Despite a strong treatment effect on arterial propionate and butyrate, the arterial insulin concentration was not affected by butyrate treatment (Table 3). It seems therefore that the drop in arterial glucose with the greatest butyrate level cannot be explained by increasing plasma insulin alone. These data suggest that propionate and butyrate directly or indirectly affect insulin sensitivity of peripheral tissues. Moreover, these data are in line with previous work (Reynolds et al., 1989; Stern et al., 1970) and add to the pool of evidence questioning the hypothesis that propionate and butyrate are important secretagogues for insulin in ruminants. Propionate and butyrate could have important regulatory functions in ruminants; however, it seems to be an oversimplification only to address such functions as mediated via systemic insulin levels.

Net Hepatic Flux
The net hepatic flux of acetate, glucose, lactate, and insulin was not different with VFA buffers compared with Control (Table 5). The net hepatic uptake of propionate, isobutyrate, butyrate, and valerate increased (P < 0.05) with VFA buffers compared with Control. The hepatic uptake of butyrate and valerate increased linearly (P < 0.05) with butyrate absorption. The net hepatic flux of glucose and lactate were not affected by buffer treatment nor was the net hepatic flux of glucose affected by presence or absence of propionate in the ruminal buffers (Table 5), which is similar to the results of previous studies (Kristensen et al., 2002; Kristensen and Harmon, 2004). The net hepatic flux of glutamate and glutamine increased (P = 0.01) with the VFA buffers, but the numerical difference was minute compared with the carbon deficit for hepatic gluconeogenesis with the Control buffer.

Portal Recovery of Ruminal VFA
The portal recovery of ruminally absorbed acetate (76 ± 6%), propionate (87 ± 6%), and isobutyrate (101 ± 9%) was not affected by buffer treatment (Table 6). The recovery of acetate was not corrected for PDV uptake of arterial acetate, and the net portal flux obtained indicated that the true unidirectional rumen-to-blood flux of acetate would fully account for all acetate absorbed from the rumen, which agrees with data from both sheep and steers (Kristensen et al., 2000a; Kristensen and Harmon, 2004). The portal recovery of ruminal propionate was similar in the present and a previous experiment (87 ± 6 vs. 91 ± 6; Kristensen and Harmon, 2004). There seems therefore to be evidence for the conclusion that approximately 10% of ruminal propionate is metabolized during absorption. Data from sheep (Kristensen et al., 2000a) also support a propionate metabolism in this range. All isobutyrate absorbed from the rumen could be accounted for in the portal vein in agreement with data from sheep (Kristensen et al., 2000a), indicating that isobutyrate is not metabolized by the ruminal epithelium during absorption.

In the current study, as well as in a previous study with sheep (Kristensen et al., 2000b) where the ruminal load of butyrate was increased and ruminal valerate absorption remained constant, the portal recovery of ruminal valerate was closely correlated to the portal recovery of ruminal butyrate. This may indicate competitive interaction in the metabolism of butyrate and valerate by the ruminal epithelium. Metabolism of VFA by the ruminal epithelium in the current study indicates that the acyl-CoA synthetase of the epithelium has a high affinity for butyrate and valerate, and a low affinity for acetate, propionate, and isobutyrate. This agrees with the properties of butyryl-CoA synthetase (EC 6.2.1.2) isolated from bovine heart mitochondria (Webster et al., 1965) that showed high catalytic activity with butyrate, valerate, and caproate, but low activity with propionate and acetate. Likewise, it has been shown that butyrate addition in vitro inhibited rumen epithelial metabolism of acetate and propionate (Ash and Baird, 1973; Harmon et al., 1991).

Data on butyrate and valerate metabolism point to the conclusion that VFA metabolized in the ruminal epithelium are activated by butyryl-CoA synthetase; however, if that were also the case for propionate, we would have expected a decreasing propionate uptake by the ruminal epithelium with increasing butyrate absorption. The relatively high arterial concentration of propionate with the high butyrate treatment makes the estimate of the unidirectional portal flux of propionate sensitive to PDV metabolism of arterial propionate. If it is assumed that 50% of the arterial propionate is taken up by the PDV, the estimate of recovery of ruminally absorbed propionate in the portal vein would be 0.93 compared with 0.83 when calculated from the net portal flux (Table 6). Also the decreasing (P = 0.01) net portal flux of lactate with increasing absorption of butyrate from the VFA buffers indicates that ruminal epithelial metabolism of propionate into lactate decreased with the high butyrate treatment and is in agreement with the hypothesis that propionate is activated by butyryl-CoA synthetase in the ruminal epithelium. However, the decreasing rumen epithelial metabolism of valerate with increasing butyrate absorption would also supply less substrate for lactate production in the ruminal epithelium.

Splanchnic Recovery of Ruminal VFA
The butyrate treatment did not affect splanchnic recovery of ruminal acetate, isobutyrate, valerate, the sum of total acetyl equivalents, or the sum of propionyl equivalents (Table 6). However, the composition of substrates supplied to peripheral tissues changed as a function of butyrate absorption. With increasing butyrate absorption, more (P < 0.01) propionate and butyrate were released to peripheral tissues as propionate and butyrate and the splanchnic lactate release decreased and accounted for less (P < 0.01) ruminal propionate. The increasing splanchnic release of propionate was caused by a decreased (P < 0.01; data not shown) hepatic extraction of propionate (0.57 ± 0.03) with the greatest butyrate level compared with hepatic extraction of 0.81 to 0.85 ± 3 with the other buffers. The hepatic extraction ratio of butyrate also decreased (P < 0.01) with increased butyrate absorption. Ricks and Cook (1981) found propionyl-CoA synthetase activity with two different fractions isolated from liver mitochondria. The authors concluded that one was a specific propionyl-CoA synthetase with narrow substrate specificity and the other was an acyl-CoA synthetase with activity in the presence of propionate and butyrate, as well as other acids. The current study adds to the pool of data showing that butyrate can affect the hepatic propionate metabolism previously shown in vivo (Krehbiel et al., 1992), as well as in vitro (Aiello et al., 1989). Thus, according to the findings of Ricks and Cook (1981), a relatively large fraction of the propionate activated in the bovine liver could be activated by the less specific acyl-CoA synthetase, whereas propionate and butyrate probably have to compete for the same active site.

The data obtained in the present, as well as in a previous study (Kristensen and Harmon, 2004), indicate that valerate is activated differently in the liver compared with the ruminal epithelium, and that the activation in the liver is unaffected by presence of propionate and butyrate. The hepatic extraction ratio of valerate increased (P < 0.01) with the VFA buffers (0.86, 0.91, and 0.93 ± 0.03 with the butyrate levels of 4, 12, and 36, respectively) compared with the Control buffer (0.74 ± 0.03), which is opposite of the effects on hepatic extraction of propionate and butyrate. The splanchnic recovery of ruminal valerate did not change (P = 0.67) with buffer treatment (Table 6), which was also reflected in the arterial concentrations of valerate remaining unaffected by level of butyrate absorption.

Effects of Increased Peripheral VFA Supply
The washed-rumen model as applied in the present experiment is not dependent on ruminal motility to ensure agitation of the ruminal buffer, and the steers will therefore not be able to downregulate VFA absorption by slowing ruminal motility. Previous studies have shown that the well-described inhibitory effect of high loads of VFA on ruminal motility (Svendsen, 1973; Crichlow, 1988) slows rumen outflow (Harmon et al., 1985) and portal absorption of VFA (Kristensen et al., 1998). It is not known whether the butyrate loads of the current study would have induced a similar response. The high butyrate absorption was not followed by any visible signs of discomfort to the animals; however, ruminal motility was not monitored, and the steers could have responded with decreased ruminal motility that during normal ruminal conditions would have modulated the ruminal absorption and perhaps decreased the effect of butyrate on PDV and hepatic metabolism.

	Implications

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The capacity for butyrate metabolism of both the ruminal epithelium and liver is limited, and the supply of excessive amounts of butyrate has a series of metabolic consequences. High butyrate loads markedly increase the proportion of absorbed butyrate and valerate transferred to the portal blood, and this is followed by an increasing amount of butyrate and propionate bypassing liver metabolism. Fresh cows rapidly increasing feed intake or other ruminants shifted to a diet that results in extensive butyrate fermentation in the rumen could be in danger of butyrate toxicity if the metabolic capacity of the ruminal epithelium is exceeded.

	Footnotes

 
¹ The Danish Agricultural and Veterinary Research Council (Grant 23-01-0156) and the University of Kentucky Agric. Exp. Stn. supported the study. Publication No. 04-07-013 of the Univ. of Kentucky Agric. Exp. Stn. The skillful assistance of J. Adamsen, C. Adkins, J. Combs, K. Hanson, B. Kitts, J. Piel, and D. True is gratefully acknowledged.

² Correspondence: Blichers Allé D20, DK-8830 Tjele (phone: +45-8999-1109; fax: +45-8999-1166; e-mail: nbk{at}agrsci.dk).

Received for publication February 17, 2004. Accepted for publication August 24, 2004.

	Literature Cited

Top Abstract Introduction Materials and Methods Results and Discussion Implications Literature Cited

 


Aiello, R. J., L. E. Armentano, S. J. Bertics, and A. T. Murphy. 1989. Volatile fatty acid uptake and propionate metabolism in ruminant hepatocytes. J. Dairy Sci. 72:942–949.

Ash, R., and G. D. Baird. 1973. Activation of volatile fatty acids in bovine liver and rumen epithelium. Evidence for control by autoregulation. Biochem. J. 136:311–319.[Medline]

Bugaut, M. 1987. Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals. Comp. Biochem. Physiol. B 86:439–472.[Medline]

Crichlow, E. C. 1988. Ruminal lactic acidosis: Forestomach epithelial receptor activation by undissociated volatile fatty acids and rumen fluids collected during loss of reticuloruminal motility. Res. Vet. Sci. 45:364–368.[Medline]

Dijkstra, J., H. Boer, J. Van Bruchem, M. Bruining, and S. Tamminga. 1993. Absorption of volatile fatty acids from the rumen of lactating dairy cows as influenced by volatile fatty acid concentration, pH and rumen liquid volume. Br. J. Nutr. 69:385–396.[Medline]

Gálfi, P., S. Neogrády, and T. Sakata. 1991. Effects of volatile fatty acids on the epithelial cell proliferation of the digestive tract and its hormonal mediation. Pages 49–59 in Physiological Aspects of Digestion and Metabolism in Ruminants. T. Tsuda, Y. Sasaki, and R. Kawashima, ed. Academic Press Inc., San Diego, CA.

Harmon, D. L., R. A. Britton, R. L. Prior, and R. A. Stock. 1985. Net portal absorption of lactate and volatile fatty acids in steers experiencing glucose-induced acidosis or fed a 70% concentrate diet ad libitum. J. Anim. Sci. 60:560–569.

Harmon, D. L., K. L. Gross, C. R. Krehbiel, K. K. Kreikemeier, M. L. Bauer, and R. A. Britton. 1991. Influence of dietary forage and energy intake on metabolism and acylcoa synthetase activity in bovine ruminal epithelial tissue. J. Anim. Sci. 69:4117–4127.[Abstract]

Harvey, R. B. and A. J. Brothers. 1962. Renal extraction of para-aminohippurate and creatinine measured by cintinuous in vivo sampling of arterial and renal-vein blood. Ann. N. Y. Acad. Sci. 102:46–54.

Huntington, G. B., C. K. Reynolds, and B. H. Stroud. 1989. Techniques for measuring blood flow in splanchnic tissues of cattle. J. Dairy Sci. 72:1583–1595.

Kramer, T., T. Michelberger, H. Gürtler, and G. Gäbel. 1996. Absorption of short-chain fatty acids across ruminal epithelium of sheep. J. Comp. Physiol. B 166:262–269.[Medline]

Krehbiel, C. R., D. L. Harmon, and J. E. Schnieder. 1992. Effect of increasing ruminal butyrate on portal and hepatic nutrient flux in steers. J. Anim. Sci. 70:904–914.[Abstract]

Kristensen, N. B. 2000. Quantification of whole blood short-chain fatty acids by gas chromatographic determination of plasma 2-chloroethyl derivatives and correction for dilution space in erythrocytes. Acta Agric. Scand. Sect. A 50:231–236.

Kristensen, N. B., A. Danfær, and N. Agergaard. 1998. Short-chain fatty acids in sheep: Portal appearance rates following high intraruminal loads. Acta Agric. Scand. Sect. A 48:165–174.

Kristensen, N. B., A. Danfær, B. A. Røjen, B.-M. L. Raun, M. R. Weisbjerg, and T. Hvelplund. 2002. Metabolism of propionate and 1,2-propanediol absorbed from the washed reticulorumen of lactating cows. J. Anim. Sci. 80:2168–2175.[Abstract/Free Full Text]

Kristensen, N. B., G. Gäbel, S. G. Pierzynowski, and A. Danfær. 2000a. Portal recovery of short-chain fatty acids infused into the temporarily-isolated and washed reticulo-rumen of sheep. Br. J. Nutr. 84:477–482.[Medline]

Kristensen, N. B., and D. L. Harmon. 2004. Splanchnic metabolism of volatile fatty acids absorbed from the washed reticulorumen of steers. J. Anim. Sci. 82:2033–2042.[Abstract/Free Full Text]

Kristensen, N. B., S. G. Pierzynowski, and A. Danfær. 2000b. Net portal appearance of volatile fatty acids in sheep intraruminally infused with mixtures of acetate, propionate, isobutyrate, butyrate, and valerate. J. Anim. Sci. 78:1372–1379.[Abstract/Free Full Text]

Le Bars, H., J. Lebrument, R. Nitescu, and H. Simonnet. 1954. Recherches sur la motricité du rumen chez les petits ruminants. IV. Action de l’injection intraveineuse d’acides gras à courte chaîne. Bull. Avad. Vet. 27:53–67.

López, S., P. D. D. Hovell, J. Dijkstra, and J. France. 2003. Effects of volatile fatty acids supply on their absorption and on water kinetics in the rumen of sheep sustained by intragastric infusions. J. Anim. Sci. 81:2609–2616.[Abstract/Free Full Text]

Manns, J. G., and J. M. Boda. 1967. Insulin release by acetate, propionate, butyrate, and glucose in lambs and adult sheep. Am. J. Physiol. 212:747–755.[Free Full Text]

Nozière, P., C. Martin, D. Rémond, N. B. Kristensen, R. Bernard, and M. Doreau. 2000. Effect of composition of ruminally-infused short-chain fatty acids on net fluxes of nutrients across portal-drained viscera in underfed ewes. Br. J. Nutr. 83:521–531.[Medline]

Oshio, S., and I. Tahata. 1984. Absorption of dissociated volatile fatty acids through the rumen wall of sheep. Can. J. Anim. Sci. 64(suppl.):167–168.

Pennington, R. J. 1952. The metabolism of short-chain fatty acids in the sheep 1. Fatty acid utilization and ketone body production by rumen epithelium and other tissues. Biochem. J. 51:251–258.

Prasad, K. N., and P. Sinha. 1976. Effect of sodium butyrate on mammalian cells in culture: A review. In Vitro 12:125–132.[Medline]

Rechkemmer, G. 1991. Transport of weak electrolytes. Pages 371–388 in Handbook of Physiology. The Gastrointestinal System IV. S. T. Schultz, M. Field, and R. A. Frizzell, ed. Am. Physiol. Soc., Bethesda, MD.

Reynolds, C. K., G. B. Huntington, T. H. Elsasser, H. F. Tyrrell, and P. J. Reynolds. 1989. Net metabolism of hormones by portal-drained viscera and liver of lactating holstein cows. J. Dairy Sci. 72:1459–1468.

Ricks, C. A., and R. M. Cook. 1981. Regulation of volatile fatty acid uptake by mitochondrial acyl CoA synthetases of bovine liver. J. Dairy Sci. 64:2324–2335.

Sakata, T., and H. Tamate. 1978. Rumen epithelial cell proliferation accelerated by rapid increase in intraruminal butyrate. J. Dairy Sci. 61:1109–1113.

Sakata, T., and H. Tamate. 1979. Rumen epithelium cell proliferation accelerated by propionate and acetate. J. Dairy Sci. 62:49–52.

Sander, E. G., R. G. Warner, H. N. Harrison, and J. K. Loosli. 1959. The stimulatory effect of sodium butyrate and sodium propionate on the development of rumen mucosa in the young calf. J. Dairy Sci. 42:1600–1605.[Abstract/Free Full Text]

Sehested, J., J. B. Andersen, O. Aaes, N. B. Kristensen, L. Diernæs, P. D. Møller, and E. Skadhauge. 2000. Feed-induced changes in the transport of butyrate, sodium and chloride ions across the isolated bovine rumen epithelium. Acta Agric. Scand. Sect. A 50:47–55.

Stern, J. S., C. A. Baile, and J. Mayer. 1970. Are propionate and butyrate physiological regulators of plasma insulin in ruminants? Am. J. Physiol. 219:84–91.[Free Full Text]

Svendsen, P. 1973. The effect of volatile fatty acids and lactic acid on rumen motility in sheep. Nord. Vet. Med. 25:226–231.[Medline]

Toivonen, E., I. Hemmilä, J. Marniemi, P. N. Jørgensen, J. Zeuthen, and Y. Løvgren. 1986. Two-site time-resolved immunofluorometric assay of human insulin. Clin. Chem. 32:637–640.[Abstract/Free Full Text]

Topping, D. L., and P. M. Clifton. 2001. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 81:1031–1064.[Abstract/Free Full Text]

Webster, L. T., Jr., L. D. Gerowin, and L. Rakita. 1965. Purification and characteristics of a butyryl coenzyme A synthetase from bovine heart mitochondria. J. Biol. Chem. 240:29–33.[Free Full Text]

Weigand, E., J. W. Young, and A. D. McGilliard. 1972. Extent of butyrate metabolism by bovine ruminoreticulum epithelium and the relationship to absorption rate. J. Dairy Sci. 55:589–597.

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