Metabolites as feedbacks for control of feed intake and receptor sites in goats and sheep

Physiology and Behavior. Vol. 7, pp. 819-826. Pergamon Press, 1971. Printed in Great Britain

Metabolites as Feedbacks for Control of Feed Intake and Receptor Sites in Goats and Sheep' C L I F T O N A. B A I L E ~

Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, Massachusetts 02115 e (Received 26 O c t o b e r 1970) BAILE, C. A. Metabolitesas feedbacksfor control of feed intake and receptor sites in goats and sheep, PHYSIOL.BEHAV. 7 (6) 819-826, 1971.---To test their role in the hunger-satiety mechanism, metabolites were injected during spontaneous meals into goats and sheep fed a grain ration ad lib. Feed intake of goats and sheep was decreased about 40 per cent by injections of 15 and 31 mM per meal, respectively, of propionate into the ruminal vein (RV), but not decreased by 21 and 50 mM per meal, respectively, into the jugular vein (JV). Injections of an average of 41 mM of propionate per minute decreased feed intake of goats about 36 per cent. Sheep injected with propionate into the carotid artery (CA) (31 mM per meal), or mesenteric (MV) (36 mM per meal), or portal veins (53 mM per meal) did not decrease feed intake significantly. In sheep, glucose (23 mM per meal) when injected into the CA decreased feed intake 35 per cent although when injected into the RV or MV had no effect. Feed intake of both goats and sheep decreased when 19 and 39 mM per meal, respectively, of butyrate were injected into the .IV. Lactate injected into the JV decreased feed intake of goats, but not sheep, despite larger injections. Sheep (but not goats) decreased feed intake during RV and JV acetate injections. It is proposed that in the ruminal region of both goats and sheep there are propionate receptors which may function in the control of feed intake. Control of feed intake in ruminants

Acetate

Propionate

RUMINANTS SHOW evidence of maintaining energy balance [10, 12, 14, 17, 22, 32] when neither caloric density [14] nor palatability [21] is a limiting factor making them similar in these aspects to other animals studied [1, 25]. Because of fermentation in their forestomachs, the possible metabolic feedbacks of a hunger-satiety mechanism may be different from those of monogastric animals. The major end-products of the fermentation processes, and thus major energy sources, are the volatile fatty acids (i.e. acetic, propionic and butyric) and, under some conditions, lactic acid. These are mainly absorbed from the forestomach regions, not from the intestines. Although each of these intermediary metabolites can decrease feed intake when injected intraruminally during spontaneous meals, acetate and propionate are most effective relative to their normal rates of production [4, 6]. Experiments with cattle have shown that feed intake can be decreased by injections of acetate [18], propionate [18, 39, 40] and butyrate [18] into the jugular vein. These injections were continuous for 7-8 hr and were not restricted to spontaneous meals. The following experiments were designed to test several important metabolites for possible function in the hungersatiety mechanism of goats and sheep and were restricted to factors acting in the vascular system as opposed to the gastrointestinal system [6, 9]. Sites of receptors for several metabolites were also studied. The animals were injected

Butyrate

Glucose

Lactate

Ruminants

during spontaneous meals of a diet on which ruminants are presumably able to regulate energy balance. MATERIALSAND METHODS During these experiments, goats and sheep were housed in a constantly lighted room maintained at 24±1°C. Each animal was locked in a stall in front of which was attached an apparatus to hold feed and water. When an animal ate, his head broke a light beam impinging on a photocell which activated relays controlling a syringe pump (Harvard Apparatus, Model 975) and event marker of a strip recorder (previously described [7]). With these apparatuses, the animals were injected during spontaneous meals to simulate metabolic changes that may occur during feeding and tbus to test possible factors which may act as feedbacks in the control of feed intake. In calculating the number of meals per day from the recorder strip charts, a meal was defined as being at least 5 min in duration and at least 30 min since the previous meal. The meal length is an estimate which includes short intervals that an animal's head was not in the feeder. Water and feed (a grain ration--Omolene X*, Ralston Purina, less than 9 per cent fiber) intakes were measured daily at 8-9:00 a.m. Goats and sheep weighed 34-4-3 and

XThis work was supported, in part, by grants-in-aid from the National Institute of Neurological Diseases and Blindness (NB-01941), the National Science Foundation (GB-7354), and by the Fund for Research and Teaching, Dept. of Nutrition, Harvard School of Public Health. ~The author is grateful for the technical assistance of Miss Carol McLanghlin and William Zinn. 8Please send reprint requests to: Smith, Kline and French Laboratories, 1600 Paoli Pike, West Chester, Penn. 18380, U.S.A. 819

820

BA I I . t

444-4 kg, 4-SEM, respectively. Probabilities were calculated from paired t-tests between preinjection and injection periods.

Effects of Metabolites Injected Intravenously on Feed Intake of Goats In these experiments goats were given 6-day treatments: 2-day pre-injection, 2-day injection and 2-day post-injection. Each treatment was replicated with each goat. In the first series of tests, solutions were injected during spontaneous meals into a catheter of Silastic tubing (obtained from G. P. Pilling Co., New York) inserted into a jugular vein of each goat. Table 1 shows the solutions injected. In a second series of tests, goats were prepared surgically under aseptic conditions with Silastic catheters in the left or right ruminal vein. The intravascular catheters, except those in the jugular vein, were routinely attached to a multisyringe pump (Harvard Apparatus, Model 100-910); by means of a timer system about 0.1 ml of 0.9 per cent saline was injected into each catheter in 15 sec every 5 min to help prevent blood clotting in the catheters. A T-connector was used so that a test solution from a separate pump could be injected during meals. To test the effect of propionate injected into the ruminal vein, goats were not injected for 2 days, then injected with 4.0 M N a propionate (pH = 7.34) for 2 days, followed by 2 days of no injection. The procedure was repeated with the same goats, but with injections into a jugular vein via Silastic catheters. In Table 1 are shown the treatments, sites of injection and average rates of injection.

TABLE 1 DESCRIPTION OF TREATMENTS

Species

Treatment

Site of Injection

Average Rate of Injection (mM/min)

Goat

4.0 M NaProp-L* 4.0 M NaProp-H* 4.0 M NaButyrt 4.0 M Nal_,act~ 4.0 M NaCI§ 2.0 M Glucll 4.0 M NaProp* 4.0 M NaProp*

J.V. J.V. J.V. J.V. J.V. J.V. J.V. R.V.

1.48 6.32 1.56 1.36 1.71 1.16 1.19 0.95

Sheep

4.0 M NaProp-L* 4.0 M NaProp-H* 4.0 M NaProp* 4.0 M NaProp* 4.0 M NaProp* 4.0 M NaProp* 4.0 M NaAcet¶ 4.0 M NaAcet¶ 4.0 M NaButyrl2.0 M Gluell 2.0 M Glucfl 2.0 M Glucl[ 4.0 M Lact~ 4.0 M Lact++

J.V. J.V. C.A. R.V. M.V. P.V. R.V. J.V. J.V. R.V. M.V. C.A. J.V. M.V.

2.51 4.67 4.68 3.01 3.62 5.23 1.41 6.17 4.64 0.89 1.79 3.08 3.51 2.82

*Purified granular, obtained from Fisher. tButyric acid, Fisher reagent, obtained from Fisher. ~:60% syrup, obtained from Fisher. §Granular, ASC specification, obtained from Fisher. IIHydrate dextrose, granular, obtained from Corn Products. ¶Granular, N.F. grade, obtained from Fisher.

Effects of Metabolites Injected lntruvaseularly ~m F~,ed Intake of Sheep Sheep were prepared surgically with catheters in the right ruminal, mesenteric, or portal veins. The ruminal vein catheters were inserted into the vein near the end of the ventral sac and extended into the vein about 10 cm. Each of the mesenteric vein catheters of one group of sheep was inserted only about 10cm. Another group of sheep had catheters inserted in either the mesenteric or cecal veins until the ends of the catheters were at the level of the portal vein. F o r other treatments, each sheep was surgically prepared with catheters in the carotid artery, directed toward the head and the artery was left patent. After the sheep recovered from surgery and were eating normally, the effect of metabolites on feed intake was tested by injections during spontaneous meals: injection of 0.9 per cent saline for 2 days, injection of a test substance for 2 days, and injection of 0.9 per cent saline for 2 days. The solutions injected, sites of injection and average rates of injection are listed in Table 1.

RESULTS

Effects of Metabolites Injected Intravenously on Feed Intake of Goats The results of injections in the jugular vein are shown in Fig. 1. Feed intake of goats was not depressed when about 21 m M per meal of N a prol~ionate were injected, but was depressed about 36 per cent when about 41 m M per meal were injected (p < 0.05). The m M injected per day during these two treatments was nearly the same, but the rate of injection was greater and there were fewer meals in the latter. (Changes in means described in this section are relative to the means for the 2-day period prior to the test injection period). Injections of only 172mM per day or about 19 m M per meal of N a butyrate depressed feed intake about 26 per cent (p < 0.02). With butyrate and the higher level of propionate, average feed intake was depressed for the 2-day period following the test injections but was in most cases normal on the second day of the period. Jugular vein injections of only 120 m M per day or 16 m M per meal of N a lactate depressed feed intake 46 per cent (p < 0.01). There was a slight depression of feed intake during the 2 days following lactate injections. Injections of 296 m M of NaC1 solution per day or about 23 m M per meal did not depress feed intake significantly; 198 m M per day or about 20raM per meal of glucose did not depress feed intake significantly. Water intakes were generally not affected b y t h e treatments although intakes increased significantly during butyrate and the lower level of propionate treatments. Small decreases in both meal frequency and meal length occurred during several treatments. In Fig. 2 are shown effects of N a propionate injected into either the jugular or ruminal veins. In this group of goats 256 m M per day or about 21 m M per meal injected into the jugular vein did not depress feed intake significantly. But N a propionate injected into the ruminal vein at the rate of 184 m M per day or about 15 m M per meal depressed feed intake of goats about 35 per cent (p < 0.02). The average feed intake of the goats during the latter treatment was still depressed for the 2 days after the propionate injection, but was normal in most cases on the second day. Water intake generally increased, but more during the jugular than ruminal

METABOLITES AND CONTROL OF FEED INTAKE OF RUMINANTS

821

I--'1 PREINJECTION (=

I~a INJECTION POSTINJECTION

•

0'

.J bJ

p<.05

p4,l

15

5

0 3O0 200

u3

=,

IOC

o E E p<.05

p<,05

_

800 r

p<.OI

p<.OI

NoBu

NoLo

NOCI

Giuc

;1='9

n,5

n=6

4O 20 ,v

C"

N,,Pr

n,15

NoPr

n='~ TREATMENT

FIG. 1. The effect on feeding behavior and water intake of goats from injections of metabolites into the jugular vein during spontaneous meals. The four solutions tested were 4.0 M Na salts of propionate (Pr, 2 levels), butyrate (Bu), Lactate (I_a) and chloride (C1) and 2.0 M glucose (Glue).

vein injections. There was no definite trend toward a change in either meal frequency or meal length, but the latter was possibly depressed during ruminal vein injections.

Effects of Metabolites Injected Intravascularly on Feed lntake of Sheep In Fig. 3 are shown the effects on feed intake of N a propionate injected into four different veins and a carotid artery. Feed intakes were not depressed by injections of propionate into the jugular vein at a lower rate (156 m M per day or 33 m M per meal) or at a higher rate (332 m M per day or 50 m M per meal) (p > 0.6). Water intakes increased (p < 0.05) about 30 per cent during the higher injection rate of propionate. When a mean of 176 m M per day or 31 m M per meal of propionate was injected into a patent carotid artery during spontaneous meals, feed intake was not depressed (p > 0.5) and water intake increased (p < 0.02) about 45 per cent.

The lack of an effect on feed intake of injections of propionate into the jugular vein or carotid artery was contrasted by a marked effect of injections into the ruminal vein. Injections of 124 m M per day (about 31 m M per meal) decreased feed intake 45 per cent (p < 0.01). Average feed intake was also depressed during the 2-day post-injection period, but was near normal in most cases on the second day. The decrease in feed intake during propionate injections is apparently due to changes mainly in the ruminal region since similar injections into the mesenteric or portal veins failed to cause a comparable decrease in feed intake. Injections of 228 m M per day or about 36 m M per meal and 288 m M per day or about 53 m M per meal into the mesenteric and portal veins only slightly decreased feed intake, 9 and 15 per cent respectively. Injections into the mesenteric vein but not the ruminal or portal veins affected water intake significantly causing an increase of about 28 per cent (p < 0.05). Meal frequency and meal length tended to decrease (p > 0.05) during propionate injections into the visceral veins.

822

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7=

25

F--I PREINJECTION INJECTION POSTINJECTION

20 t3

w

~ 15

t~

0 30O z

d I00 E

~

0 '.

~¢',1 '0|

p<.OZ

600[

,oo

z ZO0~ ~

RV n=17 n=lO TREATMENT

FIG. 2. The effect on feeding behavior and water intake of injections of 4.0 M sodium propionate into either the jugular vein (JV) or ruminal vein (RV) of goats. Preinjection, injection and postinjection periods were each 2 days.

In Fig. 4 are shown the effects of other metabolites injected during spontaneous meals of sheep. A mean of 172 m M per day (20 m M per meal) of N a acetate decreased feed intake about 20 per cent. Acetate injections into the jugular vein likewise depressed feed intake about 20 per cent (p < 0.05) when 312 m M per day (57 m M per meal) were injected. Average feed intake was slightly depressed during the postinjection period due mainly to one animal not returning to a pre-inj~tion level. About 39 m M per meal or 272 m M per day of N a butyrate injected into the jugular vein of sheep decreased feed intake about 23 per cent. Glucose injections into the ruminal vein resulted in a trend toward increased feed intake o f about 10 per cent (0.05 < p < 0.1). About 68 m M per day or 7 . 7 m M per meal of glucose were injected, Fig. 5. Glucose (133 m M per day or about 20 m M per meal) injected into the mee~nteric vein did not affect feed intake. In contrast to the little or no effects of glucose injected into ruminal or mesenteric veins, glucose injected into the carotid artery during spontanoaus meals d ~ ' e a s e d feed intake about 35 per cent (p < 0.01). About 90 m M per day or 23 m M per meal were injected. There was little effect on feed intake of sheep during N a lactate injections into either the mesenteric or jugular vein at rates of an average of 248 or 172 m M per day or 35 or 34 m M per meal, respectively. Water intake was decreased (p < 0.05) only during injections of glucose into the carotid artery, probably related to the decrease in feed intake.

DISCUSSION

Propionate most effectively decreased feed intake when injected into the ruminal vein. An equal volume of 0.9 per cent saline, equivalent mmoles of carbon (glucose), or similar quantities of N a acetate had less or no effect on feed intake compared with propionate. That mesenteric or portal vein injections of propionate did not decrease feed intake is evidence of receptors restricted to the ruminal area and not the liver. Propionate in the jugular vein depressed feed intake, if at all, only when injected at the higher rates into goats but not sheep and similar carotid artery injections did not depress feed intake of sheep; this is strong evidence that the response is not the result of a central nervous system receptor. Neither meal frequency nor length of meal were shown to increase or decrease consistently when feed intake was decreased. In these experiments, neither meal size nor rate of eating during individual meals was measured. The solutions were injected only during meals to simulate increased metabolic absorption that may occur during feeding and thus this procedure served as a test for a hunger-satiety system. However, some of the test solutions had sustained effects and their action may not have been restricted to such a system. Propionate enters the blood principally via gastric veins, especially the ruminal veins. Propionate uptake rates from the rumen in sheep fed some grain and/or hay, have been estimated at about 2.0 m M per hr per kg body weight [2, 26-29], or about 1.1 and 1.5 mM per min for the goats and sheep respectively in our experiment. (Grain diets as used in our studies possibly result in even higher rates of propionate uptake especially soon after feed is ingested). About 21 mM per meal were injected in the ruminal vein of goats during each meal during about 15 rain or at a rate somewhat above normal uptake. In our experiment with sheep, about 31 mM were injected into the ruminal vein during each meal lasting about 10 min; this rate, which was about double the normal, lasted only for short periods of time. A large proportion of the propionate transported via the ruminal vein is metabolized by the liver [15], so arterial propionate levels remain relatively low [34, 41]. In other experiments [38] N a propionate was injected at a rate of either 1 or 4 mM per min into the ruminal vein of goats weighing about 30 kg and the jugular blood propionate concentration after 10 min of injection was about 0.2 or 1.2 mM, respectively; the initial levels were 0.1 mM. Since average rates of injection into the ruminal vein in the present experiments were about 0.95 and 3.0 mM per min for the goats and sheep, respectively, probably only small increases in blood propionate followed the ruminal vein injections. Therefore, propionate injections into the ruminal vein at near physiological levels that result in large decreases in feed intake may involve a propionate receptor system which could be a component of the feed intake controlling mechanism of ruminants. The decrease in feed intake following N a acetate injection into sheep was unexpected. Previous work by Holder [23] showed that sheep adapted to a scheduled feeding did not decrease intake following appreciable amounts of acetate injected into the jugular vein. Injections into the jugular vein of his sheep raised blood acetate levels comparable to postprandial levels. Also, feed intake was not decreased by injections during spontaneous meals of Na acetate into the jugular vein of goats at very high levels (about 140 m M per

METABOL1TES AND CONTROL OF FEED INTAKE OF RUMINANTS

I"--1 PREINJECTION ~ INJECTION

¢ E z

p<.05 ~

6.0

~

2.C 0

823

(3) Most butyrat¢ absorbed from the rumen is metabolized to beta hydroxybutyrate by the ruminal ©pitholium so very little normally enters the ruminal vein blood [15]; (4) Only after the normal rumen fluid concentration is doubled or tripled is the butyrate concentration of the ruminal vein blood affected, and then very little reaches extrahepatic tissue [37]. However, a recent study shows that arterial butyrate levels of lactating sheep increase from approximately 0.02-0.06 mM during a scheduled feeding of a pelleted ration [41]. In other experiments with goats it was shown that butyrate injected into a jugular vein at a rate of 1 m M per min for 10 min (comparable to injections in the present study) caused an increase in jugular vein butyrate level from a normal of about 0.04 to 0.2 mM [38]. It may b¢ that the effect of butyrate in the vascular system decreased feed intake because it is ketogenic [35] and, thus, may decrease feed intake differently than propionate. Butyrate

i: E P>.05 1200 z_

800

z

40C

t

Or

I.z hi J

ZO

l~

PREINJECTION

~ I~

INJECTION POSTINJECTION

15 t

hi I0.0 dV LOW n-16

dV HIGH n-16

CA

RV

n,5 n=17 TREATMENT

MV

PV

n,16

n=18

FIG. 3. The effect on feeding behavior and water intake of sheep of injections of 4.0 M Na propionate injected during spontaneous meals into the jugular vein (JV, 2 levels), carotid artery (CA), ruminal vein (RV), mesenteric vein (MY), and portal vein (PV). During preinjection and post-injection periods 0.9 per cent saline was injected. The mM injected apply only to Na propionate injections, while the ml injected are for both saline and Na propionat¢ injections.

,.,

2.5

•

0

-

O" 4.0

meal or 1.4 m M per day) which probably more than doubled the ruminal vein acetate concentration during meals; but feed intake of the same goats decreased about 40 per cent when similar quantities of acetate were injected into the rumen via a cannula [7]. The rates of injection into the ruminal vein during spontaneous meals in the present experiment are well within the normal rates of acetate uptake from the rumen of 2.5-5.0 m M per min [2, 26, 27]. Sheep, therefore, appear to be much more sensitive than goats to intravenous acetate injections under our experimental conditions. Butyrate injected into the jugular vein decreased the feed intake of both goats and sheep and was one of the most effective metabolites tested. However, this metabolite was not investigated further as a factor in the control of feed intake for the following reasons: (1) Intraruminal injections of butyrate resulted in a much smaller decrease in feed intake of goats per mmole injected compared with the effect of propionate [6] (the rumen is the source of most butyrate); (2) Butyrate is produced in the rumen and absorbed at slower rates than acetate or propionate, and much lower concentrations are present in the rumen fluid (27);

2,0

i,,oo.

_z

1.0

1 2 0 0 r"

pC,.05

p<.Ol

NoA¢ JV nm6

NoBu JV n=5

aoo~40~

NoAc RV n-9

TREATMENT

FIG. 4. The effect of 4.0 M Na acetate (Ac) and Butyrate (Bu) injected during spontaneous meals on feeding behavior and water intake of sheep. The solutions were injected in either the ruminal vein (RV) or jugular vein (JV). During proinjection and postinjection periods 0.9 per cent saline was injected. The mmoles injected apply only to NaAe and NaBu injections, while the ml injected are for all injections.

824

BAILt!

injections, at the rates used in the present study, depress ruminal motility [38] which probably is at least one cause for the feed intake depression. In addition, comparable amounts of butyrate injected into the jugular vein have been shown to cause both changes in the electroencephalogram and behavior similar to that of sleep [33]; some of these changes may also be related to satiety [36]. Injection of lactate decreased feed intake in goats, but not in sheep even though the relative levels of injection were greater in the latter. It may be that sheep are either less sensitive to lactate per se or that sheep metabolize or clear lactate at a faster rate than do goats. Lactate injections into the rumen of goats during spontaneous meals decreased feed intake [6]. Lactate concentration of rumen fluid has been shown to increase rapidly during feed intake [43] and thus could be a factor in the satiety mechanism. We have shown with goats that N a lactate injected at about 1.0 m M

;=c

[~

I

PREINJECTION INJECTION

215~-

'°.°I-

0

-.J

200f [ _ ~

0

~00

t

50 25

0

--~ ~ tu x ,¢

0

3.0

p<.05

20 1.0

~z 0

i 16ooI_ p<,l

p<.OI

p<,l

8001-

r

¢~

0-

G luc RV n=4

G I u¢ MV n=4

GIuc CA n= 9 TREATMENT

Loci MV n = II

Loot

JV n=ll

FIG. 5. The effect on feeding behavior and water intake of sheep of injections of either 2.0 M glucose (Glue) or 4.0 M Na Lactate (l_act) into ruminal (RV) or me, enteric veins (MV) or carotid artery (CA). During preinjoction and post-injection periods, 0.9 per cent saline was injected. The mmoles injected apply only to Gluc and Lact injections, while the ml injected are for all injections.

per min for 10min into the jugular vein increased the concentration of blood lactate from 0.4 to 3.5 m M (unpublished results, Baile). This rate is comparable to that of the present study. The L-lactate mixture injected is not necessarily unphysiological since both isomers can be absorbed from the rumen [19]. It is questionable whether lactate may be important in the control of feed intake even for goats, but it cannot be ruled out as a safety factor to prevent an irreversible sequence of events where lactate from fermentation becomes toxic [19]. Lactate, at levels of the present study, does not inhibit ruminal motility (Unpublished results, Baile). It has been shown that injections of glucose into the jugular vein [18, 30, 42], peritoneal cavity [35], cerebral ventricles [5], or rumen [6] of ruminants do not depress but often increase feed intake. Also insulin-induced hypoglycemia failed to cause goats [8] or sheep [16] to increase their feed intake in contrast to the response of monogastric animals [20]. (Inhibition of glucose utilization induced by 2-D-deoxyglucose caused a slight increase in feed intake of apparently satiated goats [24].) Thus, there is little if any evidence of a glucose monitoring system that initiates or terminates feeding in ruminants under almost any normal conditions. Consequently, it was quite surprising that injections of glucose, but not 0.9 per cent saline or N a propionate, into the carotid artery during spontaneous meals decreased feed intake of sheep. The injection rate was about 20 m M in about 7 min or about 3 m M per rain during a meal; the utilization rate of glucose after feeding would be approximately 0.7 m M per min [3]. If we assume no utilization of the injected glucose during the period of injection and that the glucose space is about 27 per cent of body weight [13], then approximately a 30 mg per 100 ml change in blood glucose concentration during each meal occurred. The intracarotid injection could cause a much larger change in concentration in the areas of the head supplied blood by the carotid artery during the actual injection. If blood flow were approximately 0.25 1. per rain in a carotid artery, the injection would cause an average blood glucose concentration increase of about 200 mg per 100 ml. These estimated changes are not in the normal range which occurs in ruminants during feeding, since in fact, blood glucose changes little or not at all [31, 34, 41]. That injections of glucose in the ruminal or mesenteric veins at comparable rates did not decrease feed intake is of special physiological importance since this would be the normal route of exogenous glucose entry. Although the decrease in feed intake during intracarotid injection of glucose is of interest, it is doubtful that it is a component of the normal control of feed intake. The chemicals used in these experiments were of a high grade of purity, and evidence that some impurity was not the cause of the response includes the following: (1) propionate injections into the jugular, mesenteric, or portal veins or the carotid artery of larger amounts per day than that injected into the ruminal vein did not decrease feed intake; (2) in a previous study acetate of the same grade and source injected into the jugular vein of goats at rates of 3-5 times those of the present experiment with sheep did not decrease feed intake [7]; (3) lactate injected into the mesenteric or jugular veins of sheep had no effect on feed intake, while injections at lower rates depressed intake of goats; and, (4) jugular vein injections into goats or ruminal vein injections into sheep of glucose did not decrease feed intake. There apparently are some differences between goats and sheep in response to metabolites injected intravenously

METABOL1TES AND CONTROL OF FEED INTAKE OF RUMINANTS during spontaneous meals. Sheep are less sensitive than goats to lactate injections, but apparently much more responsive to acetate injections. However, both sheep and goats decreased feed intake during propionate injections into the ruminal vein. Per mmole injected, sheep are much more sensitive to propionate injection into the ruminal vein than to injections into the mesenteric or portal veins or carotid artery. This implies that the receptors for the response are in the ruminal area. Goats are much more sensitive to propionate injections especially into the ruminal vein, but also the jugular vein, than into the lumen of the rumen; but they are much more sensitive to intraruminal than intravenous injections of acetate [7]. Therefore, it is possible that on the lumen side of the ruminal wall there are receptors that respond to acetate concentration [9] and in the ruminal veins there are receptors for propionate. Sheep

825

may have receptors responsive to glucose which can inhibit feeding, and these are most likely located in the head, i.e. brain. While glucose and butyrate responses are of questionable physiological importance, the acetate and propionate responses may have physiological importance in the control of feed intake. Some of these responses may not be unique to ruminants in that intravenous injections into monkeys of solutions of N a acetate, propionate, and lactate depressed feed intake [11]. Equal mmoles of glucose or N a chloride had no significant effect on feed intake. The monkeys were obviously not utilizing the same receptor-systems as goats or sheep in those cases where the feed intake responses were restricted to changes in the rumen fluid or ruminal vein blood. Electrophysiological studies will be required to characterize the type of receptors involved.

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