nature of hunger and satiety control systems in ruminants€¦ · nature of hunger and satiety...

Nature of Hunger and Sat iety Cont ro l Systems in Ruminants

CLIFTON A. BAILE and MARY ANNE DELLA-FERA Section of Medicine

Department of Clinical Studies New Bolton Center

School of Veterinary Medicine University of Pennsylvania

Kennet Square 19348

ABSTRACT

Understanding mechanisms in control of feed intake and regulation of energy balance in the ruminant is of great importance if improvement in efficiency of production is to be continued. Although there is evidence in both ruminants and monogastrics that body energy content is regulated, under certain circumstances the system can be overridden with the result being either excessive weight gain or loss. In either case, this can lead secondarily to metabolic disturbances and inefficient production.

The regulator of body energy content is interfaced with the controller of feed intake, thus providing a means for changes in energy output to be balanced by changes in energy input. Feeding behavior can be influenced by a variety of external and internal factors; for example, sensory cues, such as palatabili ty of a feed, can either enhance or detract from its acceptance by the animal. Certain hormones and metabolites also influence feeding behavior, and gastrointestinal factors, e.g. distention, may play a role in signaling the controller of feed intake.

While it is accepted that the central nervous system is the primary site responsible for the control of feed intake and regulation of energy balance, mechanisms in receiving and compiling the information from the periphery and then generating the appropriate response are not understood. Areas in the brain, such as the hypothalamus, have been identified as sites having a primary role in hunger and satiety, and certain neural transmitter

Received July 11, 1980.

1981 J Dairy Sci 64:1140-1152

systems have been shown to be involved in information transfer. Recently, however, peptides of the central nervous system have been found to play important roles in control of feed intake; there is evidence that opiate peptides are involved in the initiation of feeding (hunger) and cholecystokinin peptides are involved in the termination of feeding (satiety). There is much yet to be learned about roles of neural peptides, but it is likely that this new information will greatly increase our understanding of the role of the central nervous system in feeding behavior.

To best use available resources, ways must be found to overcome certain limiting factors of feed intake. The ruminant is ideally suited for utilizing a variety of "waste" products as feedstuffs, but the bulk and unpalatabil i ty of many of these products precludes their extensive use. Also, in certain disease conditions and metabolic or nutritional deficiencies, feed intake often is depressed, thus further complicating the problem and resulting in poor efficiency of production. By understanding the basic mechanisms in control of feed intake and regulation of energy balance, it should be possible to develop methods of overriding limiting factors of feeding.

INTRODUCTION

Daily feed intake is often the most obvious limitation for sustained milk production (36, 23) or growth rate (19). While voluntary feed intake during early lactation may not be sufficient to meet energy demands of the high producing dairy cow (79), feed intake during later stages of a lactation period and dry period may be excessive. The negative energy balance in early lactation may contribute to the onset of

1140

HUNGER CONTROLS -- 75TH ANNIVERSARY ISSUE 1141

metabolic diseases and depressed production (70), and too great a sustained increase in the dry period can result in development of the "fat cow syndrome" (82). Use of cheaper feedstuffs often is limited by the voluntary intake of the higher producing cows. Thus, feeding behavior and maintenance of energy balance in the dairy cow play a critical role in efficient milk production.

In the discussion the term "energy balance" is used to describe the difference between metabolizable energy of feed eaten and total energy output (26). Energy balance is taken to be a condition regulated so that a certain balance is defended. Feed intake, however, is a controlled function having the nature of an "on" or "of f" response.

Hunger is a physiological and psychological state resulting in the initiation of feeding; satiew, the opposite state, results in termination of feeding. Because the central nervous system or psychic control of complex behaviors, gastrointestinal physiology, and the metabolic state of animals all play critical roles in regulation of energy balance, the area is difficult to study, and many questions remain unanswered. More comprehensive reviews on control of feeding and energy balance regulation include: ruminants (8, 54, 99), monogastrics (50), human obesity (27), and anorexia nervosa (96).

ENERGY BALANCE REGULATION

Mature domesticated ruminants have physiological mechanisms for defending an energy balance; growing animals also adjust their nutrient intake, resulting in a constant rate of growth even when many conditions are changed. Small but sustained errors in this apparent regulatory system can result in detrimental obesity, inefficient production, or emaciation. M1 of these conditions may compromise the animal's defense against metabolic disorders and infectious diseases.

Energy balance regulation is not apparent in ruminants in some situations. Because the nutrient supply is dependent on feeding behavior and associated drives, various factors, e.g., sensory cues, can override apparent in- hibitors, resulting in fat deposition above the norm. In contrast, nutritional imbalances or deficiencies, pathological conditions, metabolic disorders, or digestible energy dilute diets all

can result in sustained tissue mobilization and subsequent apparent maintenance of partially depleted fat stores. Therefore, the apparent energy balance regulator has limitations, but a preponderance of evidence supports the concept of energy balance regulation as illustrated in the following discussion.

Effects of Lactation

Lactating dairy cows increase their energy intake in response to the demands for milk synthesis (28, 32, 75), but this increase typically lags several weeks behind the increase in milk yield (52, 79). There is usually a high correlation between milk production and nutrient intake (28, 37, 38), although the diet must have a minimal caloric concentration for a given rate of milk production as demonstrated by Bull et al. (30) (Figure 1) and Murdock and Hodgson (83).

Lactating cows commonly lose body weight in early lactation, but the weight loss normally is recovered later as milk yield declines but feed intake remains high. Thus, over the entire lactation, energy demands are generally matched by intake.

R e q u i r e m e n t f o r 6 3 0 k g c o w I i

k g m i l k 8 0 0

, . : -?: . : . . , . . . : )y

6 0 0 . : . j::::?:;'?)

.'27 k g "--" I

:5 :~.) "18 k g :i~::.'~...: . . . . . . . 3 0 0 ,[ :i-i);.;,:

~ ~ "'9 g ' ' ~ : : ' D 2 0 0 i : : .

..: ) : :

100 :-/i:'= g z i .5 1.0 1.5 2 .0 2 .5 3 .0

R A T I O N D E x D ( k c a l / m l ) Figure 1. Relationship in lactating dairy cows be-

tween caloric density (kcal DE/ml) and DE intake (kcal/day/kg "Ts body weight) and the rate of milk production. From Bull et al. (30).

~ ~700

N

Journal of Dairy Science Vol. 64, No. 6, 1981

1142 BAILE AND DELLA-FERA

Responses to Changes of Heat Exchange with Environment

Heat stress causes reduced feed intake and general performance (86). Continuous heat stress may reduce feed intake to such an extent that negative energy balance results, and ruminants may not eat at all when a climatic temperature of 40°C is maintained (3, 86). Although the critical temperatures or environmental conditions at which growth or lactation are reduced by heat stress vary with species and breeds within a species, animals have a relatively uniform production rate and efficiency over a range of conditions. Under severe cold conditions, which cause increased heat loss, feed intake increases and efficiency of production is reduced (1, 80).

The influence of heat balance on feeding is demonstrated also by direct heating or cooling of internal organs. Increasing the temperature of rumen contents in cattle from the normal 38.0°C to 41.3°C with heating coils in the rumen depressed intake by 15% (56). Decreasing the temperature of the rumen of cattle by adding cold water (5°C) resulted in a decrease in body temperature (.5°C) and increased intake by 24% (8).

==

i 32

a

/ /

/ J / /

t 6~ La .~ FC*

~JUSTEO FOR I UEI~T IDIRECTLY) I FEC~ D~ 10~LI

~JUSTED FOR

I PRO~CTIVE E~ERGY

; , , , , , ,

I ~ la 14 U ~2 71

DRY MATTER DIG£STED, ~.

Figure 2. Relationship of dry matter digestibility to adjusted feed intake at two levels of milk production of lactating dairy cows based on 114 trials. In a multiple regression analysis, digestibility, fecal dry matter/454 kg body weight/day and body weight accounted for variation in feed intake of mostly roughage diets between 52 and 66% digestibility, r = .997 (P<.01), while digestibility, metabolic mass, and pro- ductive energy accounted for most variation in feed intake of diets between 67 and 80%. From Conrad et al. (36).

Effects of Diet Dilution

The most comprehensive set of observations on the relationship between the availability of energy from feeds and intake by dairy cows was reported by Conrad et al. (36). They analyzed data from 114 digestion trials, which included rations varying from all roughage (50% dry matter digestibility) to all concentrate (80% dry matter digestibility). Although a number of assumptions were made in accounting for variation between cows, it was demonstrated that lactating cows compensated for dilution of digestible energy (DE) if the digestibility of dry matter of the feed was above ca. 67% (Figure 2). Below this digestibility, DE intake declined as digestibility declined. This 67% sometimes has been given undue significance as an exact point above which energy balance can be maintained by ruminants. Conrad et al. (36) pointed out that this was applicable only for their conditions; they calculated that for higher yielding cows (28 kg fat-corrected milk/day), feed intake would not be controlled by nutr ient requirements except when dry matter digestibil-

ity was several percentage points higher than the 67% calculated for cows of moderate yield (17 kg fat-corrected milk/day).

The relationship between milk production and minimum caloric density of diets fed to dairy cows shows that the greater the production, the more dense the required diet (Figure 1) (30). These examples show that lactating cows, like sheep and growing cattle, can control intake to maintain constant DE intake as long as the diet has a DE concentration above the "critical" point, which is variable depending on the physiological demands for substrate.

Regulatory System for Maintenance of Energy Balance

Although ruminants, like other mammals, regulate energy balance under certain conditions, it is not clear what component(s) of the energy content of the body is regulated (8). The influence of the state of the lipid depot on energy balance regulation in ruminants is not understood well. Because of selection for certain traits, the "finish" that is, at least in


HUNGER CONTROLS -- 75TH ANNIVERSARY ISSUE 1143

part, related to fatness varies between species and breeds of ruminants. These differences may be the result of changes in the level at which fat depots are regulated. There is evidence that fat ruminants eat less than thin ones and perhaps are regulating their fat depots (8, 24, 84). One explanation given for this reduced intake by fat ruminants is that the enlarged fat depots physically limit gastrointestinal capacity (51). This explanation implies ' that the physical outward expansion of the abdominal cavity is limited. However, Bines et al. (24)showed that fat cows fed hay and concentrate ate less than thin cows, although the observation that the ruminal digesta load was similar in the two groups both before and after their daily feeding period implies that intake was not limited by physical capacity of the rumen. Apparently fat cows and sheep can increase their intake during lactation so that milk production is at least equal to that of lean cows. Therefore, at least with concentrated feeds, some factor(s) other than physical volume of fat must be acting to regulate energy balance. Some cows when overfed during late lactation and during the dry period develop a "fat cow syndrome", which increases the frequency of various diseases in periparturient cows (82). Decreased voluntary feeding during late gestation, which can contribute to the development of milk fever, may be the result of elevated estrogen in plasma and can be prevented by progesterone injections (20).

There must be a link between lipid depots and the central nervous system, and likely it is a humoral factor. However, the nature of the factor remains nearly as obscure as when Kennedy (67) first proposed the lipostatic mechanism.

CONTROL OF FEEDING B E H A V I O R

The smallest units of feeding are individual bites, but a more frequently studied unit of feeding behavior is the meal. Some sensory and metabolic stimuli affect feeding by changing meal frequency, while others affect feeding by changing meal size. Due to conditioning associated with feeding, factors affecting meal size in animals fed ad libitum may not be the same as those in animals adapted to a feeding schedule. While meal size varies greatly, the amount eaten in some continuum of meals must be controlled

to maintain energy balance. Signals of satiety controlling meal size must change during the course of a meal and, thus, must have short time constants compared with the signals that regulate long-term energy balance. Although many physiological func t ions change as a consequence of feeding and have been considered for possible satiety factors, only a few appear to have an influence in controlling meal size.

Sensory Cues

It appears that ruminants use the same sensory cues as other mammals for selection of feed. It is also likely that these cues play a role in initiating a meal. There is likely an interaction between sensitivity to sensory inputs and state of energy balance. Sheep, for example, may be most fastidious when nearly satiated and eat almost all plants and all parts of plants when hungry (93).

Although sensory aspects of feeding are important in feed selection and under some conditions may influence the quanti ty eaten, such as with dry feed acceptance in young calves (81), other oropharyngeal factors are probably not important . Cows in which the boli were removed from the rumen continued to eat for much longer times and consumed larger quantities of feed than during normal feeding (33). It is unlikely, therefore, that exhaustion of salivary glands or fatigue of jaw muscles limits or acts as a control for feed intake. Also, there is no evidence that a monitoring of volume of feed swallowed might influence feeding.

Gastrointestinal Factors

There i s an increase in volume of ruminal contents during feeding despite prandial increase in rate of emptying of the rumen. Campling (33) discussed the possibility that the amount eaten at a meal might be limited by capacity of the rumen. When cattle were offered feed for about 6 h/day, the increase in total weight of digesta in the rumen during this period was 48% and the increase in weight of dry matter in the rumen was 96%. The consistency of these results, considering the range of feeds and types of cattle included, supports the concept that, with roughages at least, cattle eat until a certain ruminal distention is achieved. This distention



must be variable, however, and may be acting as a safety valve to prevent distress. In the ruminant stomach there is evidence for tension receptors with various neural adaptation times. These receptors have not yet been identified histologically. Grovum (58) showed that sheep reduced their feed intake more in response to reticular distention. Thus, the actual stretch receptors for the feeding response to distention may be located in the reticulum.

Changes in osmolarity of body fluids can influence feeding behavior in ruminants. Increases in rumen fluid osmolarity from about 250 to 300 or 350 mOsm during the rapid eating of l~rge meals may lead to hyper- tonicity of body fluids and cause dramatic renal and circulatory changes. For example, Blair-West and Brook (25) showed that within 15 rain of the initiation of rapid feeding, sheep suffered from a reduced plasma volume and a rise in systolic blood pressure, probably from the transfer of Na + and water from body fluid to rumen fluid; this change activated the renin-angiotensin system. Dehydration inhibits feeding of mammals, including ruminants (95). Despite these effects on feeding, it is not likely that changes in rumen or body fluid tonicity are large enough to limit feed intake when feeding is slow or feed is taken in small meals, e.g., when access to feed is continuous.

Feeding can influence rumen fluid pH and the importance of pH on fermentation in the rumen is well known. It is likely that feed intake is depressed when rurnen fluid pH falls below 5.0 to 5.5 because of the resulting ruminal stasis. Re- ceptors sensitive to changes in pH in rumen epi- thelium have been described (62). The evidence argues against the likelihood of rumen pH as a physiological controller of intake, although under pathological conditions it may be a prin- cipal cause of an accompanying hypophagia.

Because of the importance of volatile fatty acids (VFA) in ruminant energy metabolism, their effects on feed intake have been investigated in many experiments. During and after feeding, concentrations of VFA in rumen fluid and in blood increase (34). While this change is most apparent in cattle and sheep adapted to restricted access to feed, there is evidence that smaller increases occur during and after spontaneous meals. Differences in VFA concentrations are large in different parts of the tureen for several hours after large meals because of

the relatively slow mixing in the rumen. Acetate is produced and absorbed in greatest

quantities of all VFA, and it may play a major role in the control of meal size. Intraruminal injections of acetate solutions of various concentrations before or during a scheduled meal depressed intake in cattle, sheep, and goats (8, 16). In a number of studies attempts have been made to identify receptor sites for the effect of acetate on feeding. Injections into the dorsal area of the rumen had a greater effect on intake than injections into the ventral rumen, reticulum, or abomasum (18). Exposure of as little as 5% of the total rumen to high concentrations of acetate was sufficient to decrease feeding (76). In goats, amounts of sodium acetate that depress intake, when administered into the rumen, resulted in a much smaller depression in intake when injected into the jugular vein. This suggests that on the lumen side of the rumen there are receptors sensitive to acetate that are not activated by acetate in blood (13).

A second major metabolite, propionate, also may have a role in controlling meal size. lntra- ruminally injected propionate depressed feed intake of cattle, sheep, and goats, and intravenous injections in cattle decreased intake (8, 16). Despite these similarities between effects of acetate and propionate on feeding, the receptors probably are different because similar depression in intake occurred whether propionate was injected into dorsal rumen, ventral rumen, reticulum, or abomasum (18). In addition, injections of propionate into the ruminal vein were more effective in depressing intake than were injections into the lumen of the rumen, mesenteric or portal veins, or carotid artery (16). This suggests that propionate receptors may be in the ruminal vein wails and possibly also on the luminal side of the rumen but not in liver or in brain. More recent work shows that propionate receptors may be in the liver of sheep and that these are the receptors that cause the decrease in feeding (2); no obvious explanation can be offered for the differences in the results of these experiments. lntrarumlnal injections of butyrate into goats resulted m little more than caloric compensation in feed intake (15) in contrast to effects of injections of acetate and propionate.

While an animal is eating, even when on a spontaneous meal schedule, it is possible that


HUNGER CONTROLS - 75TH ANNIVERSARY ISSUE 1145

because of increased rate of fermentation, stratification of digesta, and slow mixing in the rumen, the concentration of rumen fluid around the papilli may change substantially more than the average of the whole ingesta; thus, VFA action on receptors, either at the surface or after absorption, would be enhanced. Apparent ly acetate and propionate are effective in ruminants because of receptors in the ruminal area.

Metabolites

Glucose has long been regarded as a part of the controlling system for feeding in monogastric animals. Although severely reduced rates of utilization of glucose from insulin- induced hypoglycemia or glucose analogues like 2-deoxyglucose do cause hunger and feeding, hyperglycemia and increased glucose utilization rates have had little effect on feeding (15). In ruminants blood glucose concentration, arterio- venous differences of glucose, and, thus, probably glucose utilization rates generally have decreased rather than increased with feeding even with ruminants adapted to a single daily meal of concentrate diets (8). Deoxyglucose causes feeding in ruminants when injected peripherally (61) or intracerebroventricularly (89).

There is little evidence that glucose concentration or utilization rate has a significant role in controlling feeding in ruminants; in fact, there is much evidence to the contrary. Whether this means that the hunger-satiety system of ruminants is basically different from that of monogastric animals remains to be shown conclusively.

It has been suggested that the increase in free fat ty acids (FFA) of plasma with starvation might act as a signal to induce feeding even though F F A increase not only with energy depot mobilization but also with feeding in animals adapted to a daily feeding schedule (34). Intraduodenal injections of long-chain fat ty acids or fats in sheep depressed intake, but it was not clear whether this was due to depression in ruminoreticulum movements or to changes in blood fat ty acid composit ion (92). Therefore, little information is available to show that F F A are a cause rather than an effect of changes in feeding.

Amino acids in plasma have been considered for roles in control of feeding (10). In sheep

they decline for a few hours after a single daily feeding and then increase to a maximum about 24 h after feeding. It is unlikely that meal size of ruminants is controlled by absorbed amino acids since amino acids are absorbed mainly from the small intestine several hours after ingestion, and diets containing even 40% protein were tolerated by cattle; although blood ammonia exceeded 100 mg/100 ml, feed intake was near normal (49). In regard to imbalances of amino acids or protein deficiencies, the suckling preruminant lamb decreased its intake about 50% in response to dietary deletion of either threonine or isoleucine and when a low total protein was fed (8% of gross energy as protein and amino acids) (88). It is unlikely that the feed intake of ruminants fed balanced diets is affected directly by amino acid changes in plasma.

Hormones

Concentrations in plasma of some hormones, e.g., antidiuretic hormone, insulin, renin, change during feeding, but it is not known whether one or more of these changes af- fects feeding. When injected into sheep during spontaneous feeding, neither insulin nor growth hormone affected daily intake. Epinephrine and norepinephrine depressed intake only when injected at near lethal doses.

Glucocorticoids caused increased feed intake in sheep when injected intramuscularly over several weeks. Hydrocortisone injected intra- venously during spontaneous meals did not affect feed intake of sheep, although during the short injection periods the rate of hormone administration was 1000 times the rate at which 17 OH-corticosteriods normally are secreted in sheep (10). It is likely that corti- costeroids act indirectly on feed intake via their effect on energy metabolism.

Body Temperature

Ruminants have, relative to carnivores, a high specific dynamic action, and a substantial proport ion is due to ruminal fermentation. Blood and skin temperatures rose during feeding in both cattle (63) and sheep (77) and fell when feed was removed. Hypothalamic temperature increased when goats and sheep became active at the time of day at which feed normally was offered, even when feed was



withheld (14, 44). Conversely, intraruminal force-feeding had no effect on hypothalamic temperature. It appears, therefore, that feeding is not related causally to increased hypothalamic or peripheral temperature in ruminants.

Because changes of hypothalamic and surface temperatures during feeding are related more to nonspecific activity than to feeding, there seems to be little evidence that temperature changes per se act under most conditions as a signal for the hunger-satiety system. Hot or cold environmental conditions can influence feed intake but may involve only indirectly control of feeding through the energy balance regulatory system. Severe heat loads inhibit feeding, and this response often may be related to stress rather than to a normal signal for satiety.

ROLE OF CENTRAL NERVOUS SYSTEM

Of the various central nervous system (CNS) structures in behavioral control, the hypothalamus has been identified as one of the more important in control of feed intake. Studies in rodents involving electrical or chemical stimulation or lesioning of various hypothalamic areas have identified certain areas which appear to be important components in the system involved with control of feeding and regulation of energy balance. For example, the ventromedial hypothalamus (VMH) generally has an inhibitory effect on feeding, and lesions of this area can result in hyperphagia and obesity (60). The lateral hypothalamus (LH) appears to be responsible for initiation of feeding, and lesions of the LH result in aphagia and weight loss (91).

Evidence of a similar system for regulating energy balance in ruminants is that electrolytic lesions of the VMH but not other areas of the hypothalamus of goats caused hyperphagia (8). However, in sheep VMH lesions have not produced hyperphagia (90). Goldthioglucose did not cause VMH lesions in sheep, probably because of differences in permeabili ty of the VMH of these animals compared with mice (17). Electrolytic lesions in the LH of goats (9) and sheep (90) have caused sustained aphagia or adipsia. As in other animals electrical stimulation of the LH caused feeding in satiated goats and sheep (72) while stimulation of the VMH reduced feeding activity of goats (100).

Further evidence for existence of an energy balance regulating system for ruminants has been obtained with injections of neural depressants into the cerebrospinal fluid (CSF) in an a t tempt to suppress the inhibitory action of the medial hypothalamus on the feeding system. Feeding responses with short latency times indicate an effect on periventricular tissue, possibly of hypothalamic origin. Satiated goats, sheep, and calves eat voraciously during perfusion of the CSF with pentobarbital (12, 85). Neural depressants also cause feeding when injected directly into the medial hypothalamus of goats and sheep (11). It seems likely the VMH has an inhibitory action on feeding in ruminants similar to that in other mammals.

Although these particular areas do appear to have important roles in the control of feed intake, the neuronal mechanisms involved in the information transfer have not yet been determined. However, this interneuronal com- munication is probably via chemical neurotransmitters, and many of the traditional neurotransmitter agents have been tested for a possible role in feeding behavior.

A variety of agents injected into the brain can elicit feeding in cattle and sheep (5, 46). To date it has not been possible to delineate any series of neurotransmitters that form a feeding circuit; however, several general conclusions can be drawn from this work: 1) intraventricular injections of a adrenoceptor agonists elicit feeding in sheep much more readily than in cattle; 2) although /3 adrenoceptor agonists cause anorexia in rats, these agents elicit feeding in both sheep and cattle and at small doses relative to those effective in rats; 3) while several /3 adrenoceptor agonists will elicit feeding, it has not been possible to characterize the receptors pharmacologically a s J~l or /32 in sheep; 4) in the hypothalamus of sheep there are distinct loci that elicit feeding and have pharmacological properties of either a- or ~3-adrenoceptors; 5) feeding elicited by carbo- chol, a cholinergic agonist, is probably a stronger response in sheep than feeding elicited by adrenoceptor agonists; this elicited feeding is suppressed by atropine, a cholinergic blocker, but not by a- or ~3-adrenergic blockers; 6) feeding was elicited in both steers and wethers by intraventricular injections of 5-hydroxy- t ryptamine (5-HT) and in sheep, certain hypothalamic areas that may have been responsible


H U N G E R C O N T R O L S - 7 5 T H A N N I V E R S A R Y I S S U E 1147

for the 5-HT elicited feeding were identified (6); 7) there is little evidence of primary and secondary stages of neural circuits utilizing different putative neurotransmitters (the possibility of establishing such circuits was decreased greatly by finding loci responsive to a specific chemical dispersed throughout the hypothalamus rather than being clustered within a hypothalamic area or nucleus).

An interpretation of these characterizations is that specific agents can elicit feeding via a set of parallel systems. It is also likely that some agents act on combinations of these systems.

More recent work, however, has indicated a role for certain brain peptides as neurohormones or neurotransmitters in both hunger and satiety. The opiate peptides, the endorphins and enkephalins, have been implicated in several behavioral control systems including feeding behavior (70). Recent experiments suggest that in ruminants, an opiate peptide receptor system is involved in initiation of hunger (7).

There is even more evidence, however, for CNS peptide involvement in satiety. Cholecys- tokinin octapeptide (CCK-OP) is in high concentrations in the CNS of ruminants and is localized primarily to cortical and hypothalamic areas (45, 71). Results from recent experiments have indicated that CCK-OP may have a physiological role in satiety. When administered as a continuous lateral cerebral ventricular (LV) injection in fasted sheep, near physiological amounts of CCK-OP caused significant decreases in feed intake (Figure 3) (40, 41). The CCK-OP probably acts specifically to decrease feed intake, since neither water intakes nor body temperatures are affected (41).

Sheep fasted for increasing time required increasing doses of CCK-OP to cause equivalent decreases in feed intake; thus, CCK-OP-induced suppression of feeding interacts in an adaptive manner with energy deficit of the animal. However, under cetain conditions, effect of CCK-OP on feed intake was longer; e.g., in sheep adapted to a 6-h feeding, injection of CCK-OP throughout that period resulted in decreased cumulative feed intake for up to 2 days. Thus, it appears that more chronic elevations of CCK-OP in the CNS could result in negative energy balance (42).

Bombesin, a nonapeptide structurally differ-

160'

140.

120"

~1~ 100,

s 80.

"~ 60,

40.

20.

Inject ion of C C K - O P into the Lateral Vent r ic les of 2 h Fasted Sheep

~c ' : ~).CO Sl~m°les CCK-OP --I',- 0.04 mln --^--0.159

min 1~ 3'0 do &o I~O 2~0 TSE 29 15 15 17 19 28

Figure 3, Sheep were fasted for 2 h before injection, and feed was returned 15 rain after beginning injection. They were injected for 3 h at .1 ml/min. Treatment means without a common letter are different, AB -- P<.05, YZ -- P<.01. N=8. TSE , treatment mean standard error. From (41).

ent from CCK, has been found in both CNS and peripheral tissues (29, 97). Peripherally bombesin has both cholecystokinetic and pancreozy- minic effects but acts via its own receptors, not those of CCK. Bombesin was equally as potent as CCK-OP in suppressing feeding when injected into the LV of sheep (43); thus, there may be two CNS peptide receptor systems involved with satiety.

The strongest evidence for a role for brain CCK-OP in satiety comes from results of studies in which CCK-OP antibody solutions were administered as continuous injections into the LV of satiated sheep. The CCK-OP antisera from two sources were tested separately and compared to the control which included serum from a nonimmunized animal. Both CCK-OP antisera caused significant increases in feed intake during injection, Figure 4. These results provide strong support for the hypothesis that CCK-OP in the brain is released during feeding into the CSF, which then transports the peptide to CCK receptors responsible for initiating satiety and related physiological changes (39, 41). Much remains to be done in this area, but certain behaviors and physiological functions well may have specific peptides that are in part responsible for their control.



T 2so~ T - ' ' -

Injection , , ~ ' ° ~ / I

~2oo J:// / J" s S'' T:.- X

150 .~os.-"'"

I00 ~-~ &

50

Time (hr)

Figure 4. Lateral ventricular injection of CCK antibody (=- - - i) (24 pg CCK-OP binding capacity/min) or control (. o) (rabbit serum in SCSF) in satiated sheep (N=9). Sheep were permitted to eat for 15 rain before injections were begun. #P<.IO, *P<.05. From (39).

FACTORS L IMIT ING FEEDING

Many factors limit feed intake and alter energy balance. These factors usually act independently of energy needs of the animal and, thus, can reduce production.

Feeding drive is suppressed by apparent restrictions related to the state of the ruminoreticulum (32), palatability (57), nutritional deficiencies (48, 98), and metabolic disorders (8). In ruminants the neutral detergent factor fraction of the feed has been proposed as the major limitation to feed intake of fibrous feedstuffs (78). Pregnancy places restrictions on the energy regulatory system as a result of a significant physiological stress including severe hormonal shifts and fetal displacement of the ruminoreticulum (51, 64).

Feed intake is reduced quickly during most metabolic diseases such as pregnancy toxemia, acetonemia (70), D-lactic acidosis (47, 94), ketosis (69), or bloat (35). Most gastrointestinal disorders of either infectious or parasitic origin as well as many systemic diseases result in decreased feed intake. Mechanisms for the feeding response to these diseases probably are varied and not related to signals normally controlling feed intake. Some feeds such as tall fescue con-

rain intake-depressing components under certain conditions (65).

Many forms of stress decrease feed intake, probably for a number of reasons. Heat stress (and its effect on feed intake) is probably one of the most easily studied and documented forms. Stress caused by dehydration decreases feeding in ruminants (31).

PREDICTION OF FEED INTAKE

It remains difficult to predict with much precision the consumption of total mass, dry matter, or DE of a ruminant fed any of the many possible types of diets. Baumgardt (21) expressed nutrient value as DE per unit of volume and gave the minimum caloric density required of a feed to support given metabolic demands. For example, lactating cows require a more calorically dense feed than do nonlactating c o w s if loss of body weight is to be avoided. This system, like most others, does not include sensory effects of the feed nor does it take directly into account particle size. Baumgardt et al. (22) found that for growing wethers fed 24 rations, the variables percent dry matter, bulk density, solid density, in vitro dry matter digestibility, percent nondetergent fiber, digestion coefficient for neutral detergent fiber, and a function expressing rate of digestion in vitro of neutral detergent fiber accounted for 83% of the variation in feed intake. Taking a different approach, Forbes (52, 53) developed computer analog models describing variations in feed intake of fattening, pregnant, and lactating sheep and lactating cows using metabolic, physical, and endocrine factors. Forbes (55) described a model for predicting meal size and frequency for sheep in various physiological states. Anoth- er model included the control theory concept of lag times for correcting perturbations to a system, such as changes in body weight and rate of milk production over time, and made possible predictions of intake including both effects of recent changes in production and body conditions and performance at the time in question (79).

Because of the complexity of the control of feed intake and its interrelationship with energy balance regulation, it is not surprising that prediction equations of feed intake are only poor guides when applied to a specific situation. Environmental, managerial, and social factors as


HUNGER CONTROLS - 75TH ANNIVERSARY ISSUE 1149

well as previous feeding experience, physiological conditions (lactation, fat deposition, or growth), many physical and nutritional qualities of the feed, and various sensory inputs all can have marked effect on feed intake. For satis- factory prediction of feed intake much more information on interrelationships of the many factors controlling feeding is required.

AREAS FOR FUTURE RESEARCH

While many aspects of feeding behavior have been described, much remains to be done to develop an understanding of the satiety-hunger mechanisms. Certain aspects of selected poten- tial components of the control system for feeding have been studied extensively, e.g., VFA for feedbacks for satiety, but other important components likely remain undiscovered. It is es- pecially likely that humoral factors such as the peptides, which are just now being assessed for biological effects (e.g., 59, 66, 68), play a variety of roles in control of feeding. Even after a role for a factor is established, the physiological mechanisms in its action will need to be understood to develop a basis for utilizing the information at a practical level. Mechanisms of the apparent limitations of high fibrous diets need to be eluci- dated; this may lead to development of means of reducing this limitation.

A major problem in body weight regulation or energy balance regulation is the paucity of information on factors and mechanisms involved for any mammal. Because efficiency of production is usually so dependent on intake, many improvements in food production from animals will be possible when an understanding of this area of physiology is developed. Presently peptides in the CNS are being investigated for providing links in the regulatory system for energy balance (40, 73). The defense of adipose tissue energy stores is apparent in some species but may be obscured in those animals that are selected for "finish" or fatness. Certainly the CNS plays major roles in matching surfeit- deficit signals and the balance of the range of behaviors in which the animals can engage. The various neural pathways and interfaces of information largely remain to be described.

Methods of modifying voluntary feed intake to obtain maximal production has received some attention (19), but few methods or agents have been evaluated systematically. Methods

for modification of hunger drives in the healthy cow to produce both increases and decreases when needed would provide for greater efficiency and reduced management demands. Certain metabolic diseases could be prevented if the hunger drive could be increased to provide the needed nutrients.

Little is known about the cause of depressed intake associated with many of the disease conditions. With certain infectious and metabolic diseases the decrease in nutrient supply compromises the natural defense mechanisms. Thus, greater understanding of causes of disease-associated anorexias and methods of overriding the response should result in less loss in production of the diseased lactating cow.

A C K N O W L E D G M E N T S

Research from the authors' laboratory was supported in part by grants-in-aid from the Cooperative State Research Service of the USDA (616-15-514) and the Fund for the Study of Feeding Behavior, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania. Mary Anne Della- Fera is supported by NIH Postdoctoral Fellow- ship NS06595.

REFERENCES

1 Ames, D. R., J. E. Nellor, and T. Adams. 1971. Energy balance during heat stress in sheep. J. Anita. Sci. 32:784.

2 Anil, M. H., and J. M. Forbes. 1980. Feeding in sheep during intraportal infusions of short-chain fatty acids and the effect of liver denervation. J. Physiol. 298:407.

3 Appleman, R., and J. C. Delouche. 1958. Be- havioral, physiological and biochemical responses of goats to temperature, 0 to 40 C. J. Anita. Sci. 17:326.

4 Baile, C. A. 1974. Putative neurotransmitters in the hypothalamus and feeding. Fed. Proc. 33:1166.

5 Baile, C. A. 1975. Control of feed intake in ruminants. Page 333 in Digestion and metabolism in the ruminant. I. W. McDonald and A.C.I. Warner, ed. Proc. IV Int. Syrup. Ruminant Physiol. Univ. New England Publ. Unit, Armidale, NSW, Australia.

6 Baile, C. A., J. S. Beyea, L. F. Krabill, and M. A. Della-Fera. 1979. Intracranial injections of 5-HT and db c-AMP and feeding in sheep and cattle. J. Anita. Sci. 49:1076.

7 Baile, C. A., M. A. Della-Fera, C. L. McLaughlin, and D. A. Keim. 1980. Opiate antagonists and agonists and feeding in sheep. Fed. Proc. 39:782.

8 Baile, C. A., and M. J. Forbes. 1974. Control of



feed intake and regulation of energy balance in ruminants. Physiol. Rev. 54:160.

9 Baile, C. A., A. W. Mahoney, and J. Mayer. 1968. Induction of hypothalamic aphagia and adipsia in goats. J. Dairy Sci. 51:1474.

10 Baile, C. A., and H. F. Martin. 1971. Hormones and amino acids as possible factors in the control of hunger and satiety in sheep. J. Dairy Sci. 54:897.

11 Baile, C. A., F. H. Martin, C. W. Simpson, J. M. Forbes, and J. S. Beyea. 1974. Feeding elicited by a and /3 adrenoceptor agonists injected intra- hypothalamically in sheep. J. Dairy Sci. 57:68.

12 Baile, C. A., and J. Mayer. 1966. Hyperphagia in ruminants caused by a depressant. Science 151:458.

13 Baile, C. A., and J. Mayer. 1968. Effects of intravenous versus intraruminal injections of acetate on feed intake of goats. J. Dairy Sci. 51:1490.

14 Baile, C. A., and J. Mayer. 1968. Hypothalamic temperature and the regulation of feed intake in goats. Am. J. Physiol. 214:677.

15 Baile, C. A., and J. Mayer. 1969. Depression of feed intake of goats by metabolites injected during meals. Am. J. Physiol. 217:1830.

16 Baile, C. A., and J. Mayer. 1970. Hypothalamic centres: feedbacks and receptor sites in the short-term control of feed intake. Page 254 in Physiology of digestion and metabolism in the ruminant. Proc. 3rd Int. Symp., Cambridge, England. Oriel Press, Newcastle, England.

17 Baile, C. A., J. Mayer, B. R. Banmgardt, and A. Peterson. 1970. Comparative goldthioglucose effects on goats, sheep, dogs, rats, and mice. J. Dairy Sci. 53:801.

18 Baile, C. A., and C. L. McLaughlin. 1970. Feed intake of goats during volatile fatty acid injections into four gastric areas. J. Dairy Sci. 53:1058.

19 Baile, C. A , and C. L. McLaughlin. 1979. A review of the behavioral and physiological responses to elfazepam, a chemical feed intake stimulant. J. Dairy Sci. 49:1371.

20 Bargeloh, J. F., J. W. Hibbs, and H. R. Conrad. 1975. Effect of prepartal hormone administration on feed intake and mineral metabolism of cows. J. Dairy Sci. 58:1701.

21 Baumgardt, B. R. 1970. Control of feed intake in the regulation of energy balance. Page 235 in Physiology of digestion and metabolism in the ruminant. A. T. Phillipson, ed. Proc. 3rd Int. Symp., Cambridge, England. Oriel Press, New- castle, England.

22 Baumgardt, B. R., L. F. Krabill, J. L. Gobble, and P. J. Wangsness. 1977. Estimating feed intake for cattle, sheep and swine. In Feed composition: Animal nutr ient requirements and computeriza- tion of diets. P. V. Fonnesbeck, L. E. Harris, and L. E. Kearl, ed. u tah Agric. Exp. Sta., Utah State Univ., Logan.

23 Bines, J. A. 1976. Regulation of food intake in dairy cows in relation to milk production. Livest. Prod. Sci. 3:115.

24 Bines, J. A., S. Suzuki, and C. C. Balch. 1969.

The quantitative significance of long-term regulation of food intake in the cow. Br. J. Nutr. 23:695.

25 Blair-West, J. R., and A. H. Brook. 1969. Cir- culatory changes and renin secretion in sheep in response to feeding. J. Physiol., London 204:15.

26 Blaxter, K. L. 1962. The energy metabolism of ruminants. Hutchinson, London.

27 Bray, G., ed. 1978. Recent advances in obesity research: lI. Newman Publishing Ltd., London.

28 Brown, C. A., P, T. Chandler, and J. B. Holter. 1977. Development of predictive equations for milk yield and dry matter intake in lactating cows. J. Dairy Sci. 60:1739.

29 Brown, M. R., R. Allen, J. Villarreal, J. Rivier, and W. Vale. 1978. Bombesin-like activity -- Radioimmunologic assessment in biological tissues. Life Sci. 23:2721.

30 Bull, L. S., B. R. Banmgardt, and M. Clancy. 1976. Influence of caloric density on energy intake by dairy cows. J. Dairy Sci. 59:1078.

31 Calder, F. W., J.W.G. Nicholson, and H. M. Cunningham. 1964. Water restriction for sheep on pasture and rate of consumption with other feeds. Can. J. Anim. Sci. 44:266.

32 Campling, R. C. 1966. A preliminary study of the effect of pregnancy and of lactation on the voluntary intake of food by cows. Brit. J. Nutr. 20:25.

33 Campling, R. C. 1970. Physical regulation of voluntary intake. Page 226 in Physiology of digestion and metabolism in the ruminant. A. T. Phillipson, ed. 3rd Int. Syrup., Cambridge, England. Oriel Press, Newcastle, England.

34 Chase, L. E., P. J. Wangsness, J. F. Kavanaugh, L. E. Griel, and J. H. Gahagan. 1977. Changes in portal blood metabolites and insulin with feeding steers twice daily. J. Dairy Sci. 60:403.

35 Clarke, R.T.J., and C.S.W. Reid. 1970. Legume bloat. Page 599 in Physiology of digestion and metabolism in the ruminant. A. T. Phillipson, ed. Proc. 3rd Int. Syrup., Cambridge, England, Oriel Press, Newcastle, England.

36 Conrad, H. R., A . D. Pratt, and J. W. Hibbs. 1964. Regulation of feed intake in dairy cows. I. Change in importance of physical and physiological factors with increasing digestibility. J. Dairy Sci. 47: 54.

37 Curran, M. K., R. C. Campling, and W. Holmes. 1967. The feed intake of milk cows during late pregnancy and early lactation. Anita. Prod. 9:266.

38 Curran, M. K., R. H. Wimble, and W. Holmes. 1970. Prediction of the voluntary intake of food by dairy cows. I. Stall-fed cows in late pregnancy and early lactation. Anita. Prod. 12:195.

39 Della-Fera, M. A. 1980. Proposed roles for central nerVous system cholecystokinin in the control of food intake. Ph.D. thesis, Univ. Pennsylvania, Philadelphia.

40 Della-Fera, M. A., and C. A. Baile. 1979. Cho- lecystokinin octapeptide: continuous picomole injections into the cerebral ventricles suppress feeding in sheep. Science 206:471.


HUNGER CONTROLS -- 75TH ANNIVERSARY ISSUE 1 1 5 1

41 Della-Fera, M. A., and C. A. Baile. 1980. CCK- octapeptide in CSF and changes in feed intake and rumen motil i ty. Physiol. Behav. 24:943.

42 Della-Fera, M. A., and C. A. Baile. 1980. CCK- octapeptide injected in CSF decreases meal size and daily food intake in sheep. Peptides 1:51.

43 Della-Fera, M. A., and C. A. Baile. 1980. Struc- tural specificity of cerebral ventricularly administered CCK peptides in eliciting satiety in sheep. Fed. Proc. 39:782.

44 Dinius, D. A., J. F. Kavanaugh, and B. R. Baum- gardt. 1970. Regulation of food intake in ruminants. 7. Interrelations between food intake and body temperature. J. Dairy Sci. 53:438.

45 Dockray, G. J. 1976. Immunochemica l evidence of CCK-like peptides in brain. Nature 264:568.

46 Driver, P. M., J. M. Forbes, and C. G. Scanes. 1979. Hormones, feeding and temperature in sheep following cerebroventricular injection of neurot ransmit ters and carbachol. J. Physiol. 290: 390.

47 Dunlop, R. H., and P. B. Hammond . 1965. d-lactic acidosis of ruminants . Ann. N.Y. Acad. Sci. 119:1109.

48 Egan, A. R., and R. J. Moir. 1965. Nutri t ional status and intake regulation in sheep. 1. Effects of duodenal ly infused single doses of casein, urea, and propionate upon voluntary intake of a low protein roughage by sheep. Australian J. Agric. Res. 16:437.

49 Epstein, A. N., and P. Tei telbaum. 1967. Effect of excess dietary protein on feed intake and nitrogen metabol ism in steers. J. Anim. Sci. 42:1323.

50 Festing, M.F.W. 1979. Animal models of obesity. Oxford University Press, New York.

51 Forbes, J. M. 1970. The voluntary food intake of pregnant and lactating ruminants: a review. Brit. Vet. J. 126:1.

52 Forbes, J. M. 1977. Development of a mode/ of voluntary food intake and energy balance in lactating cows. Anita. Proc. 24:203.

53 Forbes, J. M. 1977. Interrelat ionships between physical and metabolic control of voluntary food intake in fattening, pregnant and lactating mature sheep: a model. Anim. Prod. 24:91.

54 Forbes, J. M. 1978. Models of the control of food intake and energy balance in ruminants . Page 323 in Hunger models: Quantitat ive theory of feeding control. D. A. Booth, ed. Academic Press, London.

55 Forbes, J. M. 1980. A model of the short- term control of feeding in the ruminant : effects of changing animal or feed characteristics. Appeti te 1:21.

56 Gengler, W. R., F. A. Martz, H. D. Johnson , G. F. Krause, and L. Hahn. 1970. Effect of temperature on food and water intake and tureen fermentation. J. Dairy Sci. 53:434.

57 Greenhalgh, J.F.D., and G. W. Reid. 1971. Relative palatability to sheep of straw, hay and dried grass. Br. J. Nutr. 26:107.

58 Grovum, W. L. 1979. Factors affecting the voluntary intake of food by sheep. 2. The role of

distension and tactile input f rom compar tments of the s tomach. Br. J. Nutr . 42:425.

59 Guillemin, R. 1978. Peptides in the brain: the new endocrinology of the neuron. Science 202:390.

60 Hoebel, B. G., and P. Teitelbaum. 1966. Weight regulation in normal and hypotha lamic hyper- phagic rats. J. Comp. Physiol. Psychol. 61:189.

61 Houpt , T. R. 1974. St imulat ion of food intake in ruminants by 2-deoxy-d-glucose and insulin. Am. J. Physiol. 227:161.

62 Iggo, A., and B. F. Leek. 1970. Sensory receptors in the ruminant s tomach and their reflex effects. Page 23 in Physiology of digestion and metabol ism in the ruminant . A. T. Phillipson, ed. Proc. 3rd Int. Syrup., Cambridge, England. Oriel Press, Newcastle, England.

63 Ingrain, D. L., and G. C. Whittow. 1962. Effects of variations in respiratory activity and in the skin temperatures of the ears on the temperature of the blood in the external jugular vein of the ox (Bos taurus). J. Physiol., London 163:211.

64 Jordan, W. A., E. E; Lister, J. M. Wouthy, a n d J . E. Comeau. 1973. Voluntary roughage intake by nonpregnant and pregnant or lactating beef cows. Can. J. Anita. Sci. 53:733.

65 Julien, W. E., F. A. Martz, M. Williams, and G. B. Garner. 1974. Feed intake in hereford calves infused intraperitoneally with toxic fescue extract. J. Dairy Sci. 57:1385.

66 Kostin, A. J., R. D. Olson, A. V. Schally, and D. H. Coy. 1978. CNS effects of peripherally administered brain peptides. Life Sci. 25:401.

67 Kennedy, G. C. 1953. The role of depot fat in the hypothalamic control of feed intake in the rat. Proc. Roy. Soc., London, Ser. B 140:578.

68 Knoll, J. 1979. Satiation: A highly po ten t anorexagenic substance in human serum. Physiol. Behav. 23:497.

69 Krebs, H. A. 1966. Bovine ketosis. Vet. Rec. 78:187.

70 Kronfeld, D. S. 1970. Ketone body metabolism, its control, and its implications in pregnancy toxaemia, acetonaemia, and feeding standards. Page 566 in Physiology of digestion and metabolism in the ruminant . A. T. Phillipson, ed. Proc. 3rd Int. Syrup., Cambridge, England. Orie! Press, Newcastle, England.

71 Larsson, L. -I., and J. F. Rebfeld. 1979. Localiza- t ion and molecular heterogenei ty of CCK in the central and peripheral nervous system. Brain Res. 165:201.

72 Larsson, S. 1954. On the hypothalamic organiza- t ion of food intake. Acta Physiol. Scand. 32 (Supp l . ) : l l5 .

73 Margules, D. L. 1979. Beta-endorphin and endoloxone: hormones of the au tonomic nervous sys tem for the conservation or expenditure of bodily resources and energy in anticipation of famine or feast. Neurosci. Biobehav. Rev. 3:155.

74 Margules, D. L. 1979. The obesity of middle age: a common variety of Cushing's Syndrome due to a chronic increase in adrenocort icot iophin


1 1 5 2 BAILE AND DELLA-FERA

(ACTH) and beta-endorphin activity. Neurosci. Biobehav. Rev. 3 : 107.

75 Marsh, R., M. K. Curran, and R. C. Campling. 1971. The voluntary intake of roughages by pregnant and by lactating dairy cows. Anim. Prod. 13:107.

76 Martin, H. F., and C. A. Baile. 1972. Feed intake of goats and sheep following acetate or propionate injections into rumen, ruminal pouches, and abomasum as affected by local anesthetics. J. Dairy Sci. 55:606.

77 Mendel, V. E., and G. V. Raghavan. 1964. A s tudy of diurnal temperature pat terns in sheep. J. Physiol. London 174:206.

78 Mertens, D. 1980. Fiber con ten t and nutr ient density in dairy rations. Dist. Feed Conf. Proc. 35:35.

79 Monteiro, L. S. 1972. The control of appetite in lactating cows. Anim. Prod. 14:263.

80 Moose, M. G., C. V. Ross, and W. H. Pfander. 1969. Nutri t ional and environmental relationships with Iambs. J. Anim. Sci. 29:619.

81 Morrill, J. L., and A. D. Dayton. 1978. Effect of feed flavor in milk and calf starter on feed consumpt ion and growth. J. Dairy Sci. 61:229.

82 Morrow, D. A. 1976. Fat cow syndrome. J. Dairy Sci. 59:1625.

83 Murdock, F. R., and A. S. Hodgson. 1979. Effects of roughage type and texture on milk fat secretion and body weight recovery by lactating dairy cows. J. Dairy Sci. 62:505.

84 Paguay, R., D. Francoise, and J. A. Bouchat . 1979. Long-term control of voluntary food intake in sheep. Ann. Rech. Vet. 10:223.

85 Peterson, A. D., C. A. Baile, and B. R. Baumgardt . 1972. Cerebral ventricular injections of pentobarbital, glucose and sodium chloride into sheep and calves, and feeding. J. Dairy Sci. 55:822.

86 Ragsdale, A. C., H. J. Thompson , D. M. Worstell, and S. Brody. 1950. Environmental physiology with special reference to domestic animals. 9. Milk product ion and feed and water consumpt ion responses of Brahman, Jersey, and Holstein cows to changes in temperature, 50 ° to 105°F and 50 ° to 8°F. Missouri Univ. Agric. Exp. Sta. Res. Bull. 460.

87 Rehfeld, J. F. 1978. Immunochemica i studies on cholecystokinin. II. Distribution and molecular

heterogeneity in the central nervous system and small intestine of man and dog. J. Biol. Chem. 253:4022.

88 Rodgers, (2. R., and A. R. Egan. 1975. Amino acid imbalance in the liquid-fed lamb. Australian J. Biol. Sci. 28:169.

89 Seoane, J. R., and C. A. Baile. 1972. Effects of intraventricular (III ventricle) injections of 2-deoxy-d-glucose, glucose and xylose on feeding behavior of sheep. Physiol. Behav. 9:423.

90 Tarttelin, M. F., and F. R. Bell. 1968. The effects of hypothalamic lesions on food and water intake in sheep. In 3rd Int. Conf. Regulation of Food and Water Intake. Haverford College.

91 Teitelbaum, P. 1961. Disturbances in feeding and drinking behavior after hypotha lamic lesions. Page 39 in Nebraska Symp. on Motivation. M. R. Jones, ed. University of Nebraska Press, Lincoln.

92 Titchen, D. A., C.S.W. Reid, and P. Vlieg. 1966. Effects of intra-duodenal infusions of fat on the food intake of sheep. Proc. New Zealand Soc. Anim. Prod. 26: 36.

93 Tribe, D. W. 1952. The relation of palatability to nutritive value and its importance in the utilization of herbage by grazing animals. Proc. 6th Int. Grassl. Congr. 2:1265.

94 Uhart , B. A., and F. D. Carroll. 1967. Acidosis in beef steers. J. Anim. Sci. 26:1195.

95 Utley, P_ R., N. W. Bradley, and J. A. Boling. 1970. Effect of restricted water intake on feed intake, nutr ient digestibility and nitrogen metabolism in steers. J. Anim. Sci. 31:130.

96 Vigersky, R., ed. 1977. Anorexia nervosa. Ravin Press, New York.

97 Villarreal, J. A., and M. R. Brown. 1978. Bom- besin-like peptide in hypotha lamus: chemical and immunological characterization. Life Sci. 23: 2729.

98 Weston, R. H. 1971. Factors limiting the intake of feed by sheep. 1. The significance of palatability, the capacity of the al imentary tract to handle digesta, and the supply of glucogenic substrate. Australian J. Agric. Res. 22: 307.

99 Weston, R. H. 1980. Feed intake regulation in the sheep. (In press).

100 Wyrwicka, W., and C. Dobrzecka. 1960. Relation- ship between feeding and satiation centers of the hypotha lamus . Science 132:805.


nature of hunger and satiety control systems in ruminants€¦ · nature of hunger and satiety...

Documents