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Effects of adding valerate, caproate, and heptanoate to ruminal buffers on splanchnic metabolism in steers under washed-rumen conditions¹

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

^* Department of Animal Health, Welfare and Nutrition, 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 VFA absorption from bicarbonate buffers incubated in the washed reticulorumen, and metabolism by splanchnic tissues. Portal and hepatic vein blood flows were determined by infusion of p-aminohippurate into the mesenteric vein. The steers were subjected to four experimental treatments in a Latin square design. The treatments were Control (ruminal bicarbonate buffer with [mmol/kg]: acetate = 72; propionate = 30; isobutyrate = 2.1; butyrate = 12; valerate = 1.2; caproate = 0; and heptanoate = 0); Val (same as control except for valerate = 8 mmol/kg); Cap (same as control except for caproate = 3.5 mmol/kg); and Hep (same as control except for heptanoate = 3 mmol/kg). All buffers were incubated for 90 min in the rumen, and ruminal VFA absorption rates were maintained by continuous intraruminal infusion of VFA. The arterial concentrations of valerate and heptanoate showed a small increase (1 µmol/L; P < 0.05) with inclusion of the respective acid in the ruminal buffer, but no change (P = 0.57) in arterial concentration of caproate was detected. Valerate increased (P < 0.05) the net portal flux of butyrate and valerate, as well as the net splanchnic flux of propionate, butyrate, and valerate. With Cap and Hep, the net portal flux of caproate and heptanoate accounted for 54 and 45% of ruminal disappearance rates, respectively, indicating that these acids were extensively metabolized by the ruminal epithelium. Caproate was ketogenic both in the ruminal epithelium and in the liver, and Cap increased (P < 0.05) the arterial concentration, ruminal vein minus arterial concentration difference, net hepatic flux, and net splanchnic flux of 3-hydroxybutyrate. The net hepatic flux of glucose decreased (P = 0.02) with Cap and Hep compared with Control and Val; however, no effect (P = 0.14) on the net splanchnic flux of glucose could be detected. We conclude that the strong biological activity of valerate, caproate, and heptanoate warrant increased emphasis on monitoring their ruminal presence and their potential systemic effects on ruminant metabolism.

Key Words: Cattle • Hexanoic Acid • Metabolism • Short-Chain Fatty Acids • Valeric Acid

	Introduction

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A substantial amount of research has focused on the physiological functions of butyrate in gut epithelia (Topping and Clifton, 2001) and the importance of butyrate for healthy epithelia and forestomach development in calves (Baldwin et al., 2004). Nonetheless, previous studies with sheep and steers showed metabolic interactions between butyrate and valerate, indicating that these acids compete for the same metabolic pathways in the ruminal epithelium (Kristensen et al., 2000a; Kristensen and Harmon, 2004a). So far, only the effects of increasing ruminal butyrate have been studied. If butyrate and valerate are truly competing in the ruminal epithelium, increasing absorption rates of valerate will affect butyrate metabolism. Caproate and heptanoate are present in ruminal fluid in lower concentrations than shorter-chain VFA (Bergman, 1990); however, these VFA also might interact with butyrate metabolism or have direct effects on other organs, as exemplified by the inhibition of hepatic gluconeogenesis by caproate in vitro (Chow and Jesse, 1992). It is hypothesized that the metabolism of valerate, caproate, and heptanoate interacts with butyrate and thereby affects splanchnic metabolism in ruminants both indirectly and directly. Knowledge of the metabolism of specific products of ruminal fermentation might be important when addressing metabolic implications of ruminal fermentation patterns. The aim of the present study was to study the effects of including valerate, caproate, or heptanoate in ruminal VFA buffers on portal-drained visceral (PDV) and hepatic net fluxes and metabolism of VFA, glucose, lactate, 3-hydroxybutyrate, glutamate, glutamine, and insulin in steers under washed-rumen conditions.

	Materials and Methods

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All procedures involving animals were approved by the University of Kentucky Animal Care and Use Committee.

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 ruminal facies visceralis.

The steers were sampled 64 ± 2 d after surgery at an average BW of 286 ± 5 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% (vol/vol) benzyl alcohol.

Steers were fed 3.4 kg of DM/d of mixed grass hay and 3.3 kg of 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 diet provided 17.8 Mcal of ME/d (NRC, 2001). 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 also 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 steer was weighed and continuous infusion of p-aminohippuric acid (pAH; 16.9 ± 0.3 mmol/h; Sigma-Aldrich Corp., St. Louis, MO) into the mesenteric vein was initiated using a peristaltic pump (Minipuls 2, Gilson Medical Electronics, Middleton, WI). The infusate was prepared the day before sampling by dissolving pAH (250 mmol/kg of infusate) in sterile water (The Butler Co., Columbus, OH). The pH was adjusted to 7.4 and the infusate was transferred to an autoclaved bottle by sterile filtration (0.2-µm Nalgene sterile filter, Nalge Nunc Int., Rochester, NY). The infusion rate was determined gravimetrically, and the infusion solution was weighed multiple times during the infusion to ensure that the infusion rate was constant throughout the sampling day.

Washed-Rumen Procedure

After the i.v. infusion was initiated, the rumen was emptied and washed approximately three times with 5 L of warm tap water and 10 L of saline. The ruminal contents were stored in a plastic barrel and warmed before reintroducing them back to the steer at the end of the day. The steers were subjected to four treatments in a Latin square design (Control, Val, Cap, Hep; Table 1), and all four treatments were administered within a sampling day. Treatments were arranged in a Latin square, so that all steers received each treatment once, and so that all treatments occurred once as the first, second, third, and fourth ruminal buffer treatment during the course of a sampling day. The control treatment was prepared to supply the steers with normal physiological absorption rates of VFA (Kristensen and Harmon, 2004b); Val was added valerate, Cap was added caproate, and Hep was added heptanoate (Table 1). The acidity of the buffer system was balanced by decreasing the acetate concentration equivalent with adding other acids. Fifteen kilograms of the respective buffer was incubated for 90 min in the rumen along with continuous intraruminal infusion of ruminal infusate (1,021 ± 12 g/h; Table 1). The ruminal infusate containing heptanoate did not form a stable solution and was stirred by a magnetic stir bar during infusion. 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% CO₂:25% 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, placed back into the rumen, and the steer was fed.

Blood samples were obtained by simultaneously drawing blood from the artery, portal vein, hepatic vein, and ruminal catheters into 20-mL syringes flushed with a heparin solution (10,000 IU of heparin/mL). Blood was sampled 30, 60, and 90 min after initiation of the buffer incubations. Blood samples were placed on ice immediately after collection. Packed cell volume was determined by centrifugation of capillary tubes (3 min; Autocrit Ultra 3, Becton Dickinson, Franklin Lakes, NJ). Blood plasma was separated by centrifugation (2,500 x g at 4°C for 20 min), stored below –20°C, and kept on dry ice when transported between laboratories.

Ruminal buffer samples (20 mL) were obtained after 30-, 60-, and 90-min buffer incubations. Samples also were 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). Volatile fatty acid concentrations in infusates, buffers, and plasma were analyzed by gas chromatography of 2-chloroethyl esters as previously described (Kristensen, 2000). Caproate and heptanoate in buffers, ruminal, and plasma samples were determined as ethyl esters following derivatization with ethyl chloroformate, using the procedure described by Kristensen et al. (2000b). Plasma insulin was determined as described by Toivonen et al. (1986).

Calculations and Statistical Procedures

Data for lactate, glucose, glutamine, glutamate, 3-hydroxybutyrate, and insulin are reported as plasma concentrations and plasma fluxes. Blood flow rates and fluxes of VFA including caproate and heptanoate 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 portal blood or plasma flow_ij x (portal concentration_ij – arterial concentration_ij), using either whole blood or plasma values as indicated, with i = steer 1 to 4, and j = sample 1 to 12. 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:

The fractional rumen absorption rates were calculated as:

All statistical analyses were conducted on means within treatment and steer. There were no missing observations. Effects of buffer treatment on ruminal variables, arterial concentrations and flux data were analyzed as a Latin square using the GLM procedure of SAS (SAS Inst., Inc., Cary, NC). The model included treatment, steer, and period (treatment sequence within sampling day). Treatment means were separated using the PDIFF option when an overall treatment effect (P < 0.05) was detected. Significance was declared for P < 0.05, with a tendency at 0.05 P < 0.10. Means ± SEM in the text are based on four steers.

	Results and Discussion

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Ruminal Variables

The ruminal disappearance rates of acetate, propionate, isobutyrate, and butyrate (Table 2) were not affected (P = 0.37 to P = 0.84) by treatment. The ruminal valerate disappearance increased (P < 0.01) with the Val treatment, and the increase in valerate absorption (82 mmol/h) was close to the increase in infusion rate (85 mmol/h). The caproate and heptanoate disappearance rates were 114 and 120% of their infusion rates, respectively. Ruminal pH was not affected by treatment (P = 0.94). The fractional ruminal absorption rates (i.e., the proportion of the ruminal pool of the individual VFA absorbed per hour) of acetate, propionate, isobutyrate, and butyrate were not affected (P = 0.23 to 0.73) by treatment, and were similar to the previously reported values when compared at the same level of ruminal butyrate (12 mmol/kg; Kristensen and Harmon, 2004a). Increased ruminal concentrations of valerate and caproate decreased (P < 0.01) the fractional absorption rate of valerate from the rumen compared with Control and Hep (Table 2). In a previous study, we observed that increasing ruminal butyrate decreased the fractional absorption rate of valerate, and we speculated that the reason would be a saturation of epithelial metabolism followed by an increase in serosal valerate concentration and a decreased valerate gradient across the epithelium (Kristensen and Harmon, 2004a). However, the decreasing fractional absorption rate of valerate with Cap seems to have been caused by other factors because Cap did not affect epithelial valerate metabolism. Therefore, it seems unlikely that Cap would affect the transepithelial valerate gradient. A decrease in the fractional absorption rate of butyrate could not be detected with Val, but the fractional absorption rate of butyrate was numerically less with Val. The fractional absorption rates of both caproate and heptanoate were greater than expected, explaining why these acids were absorbed at 114 and 120% of their infusion rates, respectively.

The packed cell volume and the arterial concentrations of acetate, caproate, pAH, lactate, glutamine, and insulin were not affected by treatment (P = 0.29 to 0.68; Table 3). The arterial concentration of propionate tended (P = 0.08) to increase with Val. The arterial concentration of isobutyrate was less (P < 0.01) for Control than for the other treatments. The arterial concentrations of butyrate and valerate were greatest (P < 0.05) with Val, and the arterial concentration of heptanoate increased (P = 0.01) with Hep; however, the numerical changes of both valerate and heptanoate were small (0.5 to 1 µmol/kg). No change in the arterial concentration of caproate could be detected with Cap. These data indicate that splanchnic metabolism can mask substantial changes in ruminal production of longer-chain VFA. The arterial glucose concentration increased (P < 0.05) with Val compared with Control and Cap, and the concentration with Hep also was greater than for Control, but was not different from Cap and Val. The effects on plasma glucose concentration are in line with our previous studies, showing that glucose increases under washed-rumen conditions in steers when a VFA buffer is compared with a bicarbonate buffer without VFA (Kristensen and Harmon, 2004b), and a linear decrease in glucose was found with increasing butyrate absorption (Kristensen and Harmon, 2004a). In the present study, the glucogenic substrates, valerate and heptanoate, induced an increased arterial glucose concentration compared with Control and Cap. These changes in glucose concentration did not correlate well to the arterial insulin concentrations.

The portal, hepatic, or hepatic arterial blood flows were not affected (P = 0.28 to 0.58) by treatment. The portal blood flow was on average 79 ± 4% of the hepatic blood flow, and the relationship between portal and hepatic blood flow was not affected by treatment (P = 0.68). The ruminal vein blood flow was estimated from the concentration difference of isobutyrate between the ruminal vein and the artery (data not shown). It was assumed that all isobutyrate absorbed from the rumen entered the ruminal vein (Kristensen and Harmon, 2004a), and that a sample from the right ruminal vein is representative for all the blood draining the reticulorumen. The ruminal vein blood flow obtained under these assumptions was 247 ± 15 kg/h, which is equivalent to 41 ± 2% of the portal blood flow. This estimate agrees with the range of 20 to 46% reported by Barnes et al. (1986); however, the net ruminal flux of propionate calculated using this blood flow and the ruminal minus arterial concentration difference for propionate was numerically greater than the net portal flux of propionate. We assume that the ruminal vein blood flow was slightly overestimated by this approach and, therefore, no data are reported on net ruminal vein nutrient fluxes.

Net Portal Flux

The net portal fluxes of acetate, propionate, and isobutyrate were not affected (P = 0.47 to P = 0.75) by treatment (Table 4). The net portal flux of butyrate increased (P < 0.01) from 38 to 69 ± 2 mmol/h with Val compared with Control. If it is assumed that the net portal flux of butyrate is 9 mmol/h without VFA absorption from the rumen (Kristensen and Harmon, 2004a), then the portal recovery of butyrate disappearing from the rumen increased from 25% with Control to 52% with Val. The increased valerate concentration and ruminal disappearance of valerate in the present experiment affected the portal recovery of butyrate as much as did the increased ruminal butyrate concentration (12 to 36 mmol/kg) in a previous study (Kristensen and Harmon, 2004a). The net portal appearance of butyrate tended to increase with Cap and increased (P < 0.05) with Hep; however, the numerical increase was relatively small compared with Val. The net portal flux of valerate increased (P < 0.01) with Val compared with all other treatments. If the portal recovery of valerate is calculated under the assumption that the net portal valerate flux is 1 mmol/h without VFA in the ruminal buffer (Kristensen and Harmon, 2004a), then 54% of the valerate disappearing from the rumen was recovered with Val compared with 24% with Control. These data agree with our hypothesis that there are competitive interactions between the metabolism of butyrate and valerate in the ruminal epithelium; however, the total epithelial metabolism of butyrate + valerate carbon did not increase with the increased valerate absorption (417 to 441 mmol carbon/h with Control and Val, respectively). In a previous experiment (Kristensen and Harmon, 2004a), where a similar relative change in portal recovery of butyrate and valerate was obtained by increasing ruminal butyrate, the increased ruminal absorption of butyrate was followed by an increased loss of carbon across the epithelium (372 vs. 664 mmol carbon/h). These differences in the overall epithelial metabolism could indicate that there are differences in the epithelial capacity for metabolism of butyrate and valerate, which are perhaps caused by limited capacity for metabolism of propionyl-CoA from ß-oxidation of valerate. Inclusion of caproate and heptanoate in the ruminal buffer was followed by an increased (P < 0.01) net portal flux of caproate and heptanoate, respectively; however, the total epithelial metabolism of butyrate, valerate, caproate, and heptanoate carbon increased with Cap (551 mmol/h) and Hep (606 mmol/h) relative to Control (417 mmol/h) and Val (446 mmol/h). In agreement with the increased total carbon metabolism by the epithelium following Cap and Hep, the net portal flux of butyrate was not affected to the same extent as with Val. It is noteworthy that Hep and not Cap increased the net portal flux of butyrate compared with Control. With heptanoate and valerate, the epithelium is exposed to fatty acids with an uneven-numbered carbon chain leaving the epithelium, with a propionyl-CoA as the final product of ß-oxidation. These data support the idea that the limiting step in the epithelial butyrate metabolism must be early in the pathway, perhaps at the level of butyryl-CoA synthetase. If epithelial ß-oxidation was limiting butyrate metabolism, we would have expected to observe similar increases in butyrate absorption for Cap and Hep.

Net Hepatic Flux

The net hepatic flux of acetate tended (P = 0.09) to be lower with Hep compared with Control. The net hepatic flux of propionate and isobutyrate were not affected (P = 0.73 to 0.87) by treatment. The hepatic uptake of butyrate and valerate increased (P < 0.01) with Val compared with the other treatments. The net hepatic uptake of caproate and heptanoate increased (P < 0.01) when the respective acid was included in the ruminal buffer. The liver cleared 100% of the increased portal net flux of heptanoate with Hep, 100% of the increased net portal flux of caproate with Cap, and 96 and 59% of the increased net portal flux of valerate and butyrate, respectively, with Val (Table 4).

The net hepatic glucose flux decreased (P = 0.02) 24% with Cap and Hep compared with Control and Val. In vitro, hepatic gluconeogenesis from propionate has been found to decrease when ovine hepatocytes were incubated with 1 mM of caproate (Chow and Jesse, 1992). Because of similar inhibitory effects of butyrate in vitro (Aiello et al., 1989; Chow and Jesse, 1992), it was assumed that butyrate and caproate affected hepatic gluconeogenesis by the same mechanism. In vivo, however, we have not been able to show any short-term effects on net hepatic glucose flux by manipulating the hepatic uptake of any VFA in the range from acetate to valerate. Regardless of whether we removed all ruminal VFA absorption (Kristensen and Harmon, 2004b) or increased the ruminal butyrate absorption three times (Kristensen and Harmon, 2004a), the hepatic net flux of glucose did not change. The data from the present study indicate that the effects of caproate and heptanoate on liver metabolism differ from the metabolic effects of VFA with a shorter chain length. The decreased hepatic net flux of glucose was seemingly not caused by a decreased uptake of gluconeogenic substrates because the net hepatic flux of propionate, lactate, glutamate, and glutamine was not affected (P = 0.31 to 0.73) by treatment. In addition, the net hepatic flux of insulin was not affected (P = 0.19) by treatment. The net hepatic flux of 3-hydroxybutyrate increased (P < 0.01) with Cap; however, no change could be detected with Hep or Val compared with Control. The limited range of metabolites included in this study does not reveal the total picture of hepatic metabolism and mechanisms underlying the effects of caproate and heptanoate on hepatic glucose output. It is noteworthy, however, that the liver very efficiently extracted caproate and heptanoate from blood. Moreover, the increased plasma glucose concentration with Val and the tendency with Hep (Table 3) are interesting in that these changes were not correlated with the hepatic glucose output. The efficient clearance of caproate and heptanoate by the liver indicates that the apparent change in the glucose affinity by peripheral tissues, and perhaps the change in liver metabolism, could be mediated via signaling from the ruminal epithelium or the liver. Very little if any caproate and heptanoate are released to the peripheral blood, and these acids would therefore not be able to induce metabolic effects by direct stimulation of the pancreas or other tissues.

Net Splanchnic Flux

The net splanchnic flux of acetate, caproate, and insulin was not affected (P = 0.19 to 0.87) by treatment. The net splanchnic flux of caproate did not differ from zero with any of the treatments. The net splanchnic flux of propionate and valerate increased (P < 0.01) with Val compared with other treatments. The net splanchnic flux of isobutyrate tended (P = 0.05) to decrease with Cap, and heptanoate increased (P = 0.02) with Hep. The net splanchnic flux of butyrate increased (P < 0.05) with Hep compared with Control, and it was greater (P < 0.01) with Val than with any of the other treatments (Table 4). The net splanchnic flux of 3-hydroxybutyrate increased (P < 0.01) with Cap compared with all other treatments, and glutamine tended to increase (P = 0.06) with Val and Cap. The net splanchnic flux of glucose, lactate, glutamate, and insulin was not affected by treatment (P = 0.10 to 0.37). The splanchnic glucose response was less consistent than the hepatic glucose response to caproate and heptanoate, but it largely reflected hepatic glucose output.

Hepatic Extraction

The hepatic extraction ratios of acetate, isobutyrate, valerate, caproate, glucose, lactate, glutamate, glutamine, and insulin were not affected (P = 0.12 to 0.87) by treatment (Table 5). The hepatic extraction ratio of propionate decreased (P < 0.05) with Val compared with other treatments. With Cap, the hepatic extraction ratio of propionate also decreased (P < 0.05) compared with Control. Valerate does not affect hepatic propionate uptake in vitro (Aiello et al., 1989), and it seems likely that the decrease in hepatic propionate extraction with Val was caused by the inhibition of ruminal epithelial butyrate metabolism by valerate leading to an increased butyrate load on the liver. In the liver, butyrate has a relatively strong inhibiting effect on propionate metabolism in the short term (Aiello et al., 1989; Kristensen and Harmon, 2004a). The data are less clear as to whether caproate or butyrate explains the relatively small decrease (P < 0.05) in the hepatic extraction of propionate with Cap. There was a small numerical increase in the net portal flux of butyrate with Cap. Although the effects of butyrate and caproate cannot be truly separated, the fact that Hep was followed by a numerically higher net portal flux of butyrate and a smaller decrease in hepatic extraction of propionate could indicate that caproate caused a slight decrease in hepatic propionate extraction. The hepatic extraction ratio of butyrate decreased (P < 0.05) with Val compared with Control and Cap, indicating that butyrate extraction by the liver decreases with an increased hepatic load of butyrate, which agrees with previous observations (Kristensen and Harmon, 2004a). The hepatic extraction ratio of caproate and heptanoate in treatments other than where these acids were infused are based on small concentration differences across the liver and should be interpreted with caution. Nonetheless, it seems remarkable that caproate with Cap had the highest hepatic extraction of all acids tested, and the liver thereby efficiently prevents this acid from entering the peripheral circulation. We could speculate that this high affinity for caproate as well as the high liver affinity for valerate and heptanoate is a key detoxifying property of the splanchnic bed.

	Implications

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	Footnotes

 
¹ The Danish Agricultural and Veterinary Research Council (Grant 23-01-0156) and the Kentucky Agr. Exp. Stn. supported the study. Publication No. 05-07-011 of the Kentucky Agr. 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 (e-mail: nbk{at}agrsci.dk).

Received for publication February 2, 2005. Accepted for publication April 21, 2005.

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