Physiology&Behavior,Vol.52, pp. 815-817, 1992
0031-9384/92$5.00 + .00 Copyright© 1992PergamonPressLtd.
Printed in the USA.
BRIEF COMMUNICATION
Feeding Behavior in Rats Fed Diets Containing Medium Chain Triglyceride M I T S U H I R O F U R U S E , l Y A N G - H O C H O I , R E M E D I O S T. M A B A Y O A N D J U N - I C H I O K U M U R A
Laboratory of Animal Nutrition, School of Agriculture, Nagoya University, Nagoya 464-01, Japan Received 26 August 1991 FURUSE, M., Y.-H. CHOI, R. T, MABAYO AND J.-I. OKUMURA. Feedingbehavior in ratsfed diets containing medium chain triglyceride. PHYS1OL BEHAV 52(4) 815-817, 1992.--The effect of dietary medium chain triglyceride(MCT) on shortterm food intake was compared with the effect of long chain triglyceride(LCT) in rats. Corn oil and glyceryltricaprylate were used as LCT and MCT sources, respectively. Rats were given diets containing 200 g MCT/kg diet (MCT diet), 100 g MCT + 100 g LCT/kg diet (ML diet), or 200 g LCT/kg diet (LCT diet) in Experiment 1. Cumulative food intake was determined every h for the first 12 h, then at 2-h intervals thereafter during the subsequent 12 h. As early as 1 h after feeding, cumulative food intake significantlydecreased in MCT-fedanimals in a dose-dependent fashion. In Experiment 2, rats were given a choice between MCT and LCT diets for 1 h to confirm whether or not the palatability of diets was influenced by dietary fat sources. There was no difference in food intake between the two diets. In Experiment 3, the responsibilityof endogenous cholecystokinin(CCK) for the difference in food intake between the two diets was investigated for 6 h by using a CCK-A receptor antagonist, Devazepide (DVZ, 1 mg/kg b. wt.). Food intake in the MCT diet and also in the LCT diet was improved by DVZ. it is concluded that the satiety, but not the palatability, is affected by carbon chain length in dietary triglyceridesources, although the responsibilityof endogenous CCK is very small. Medium chain triglyceride
Food intake
Rat
Devazepide
MEDIUM chain triglyceride (MCT), in which fatty acids have carbon chain length from 6 to 12, is different from long chain triglyceride (LCT) in nutritional characteristics. For instance, cholecystokinin (CCK) secretion in rats was drastically enhanced by dietary MCT compared with dietary LCT (2). Cholecystokinin is known to be a satiety hormone (5). Recently, Weiler et al. (13) confirmed that endogenous CCK also played a significant role in feeding behavior. In fact, dietary MCT decreased food intake in chicks (3) and plasma CCK level was enhanced by dietary MCT vs. dietary LCT (Mabayo, Furuse, Yang, and Okumura, unpublished data). Whether or not feeding behavior in rats is affected by dietary MCT has not been investigated in a short-term period. Therefore, the present study was conducted to investigate food intake of rats given diets with two different MCT levels. Furthermore, the palatability and the responsibility of endogenous CCK were also determined.
by weight and divided into experimental groups in order to distribute body weight as uniformly as possible. Body weights (g) were: MCT group 174.5 (mean) _+ 3.52 (SEM); MCT + LCT group 174.3 _+ 3.33; LCT group 174.5 _+ 3.38 in Experiment 1. The numbers of replicates were four per diet in Experiment I. In Experiment 2, five rats (body weight, 169.4 _+ 4.34 g) were used for a choice feeding. In Experiment 3 body weights (g) were: MCT diet with vehicle 164.6 _+ 5.56; MCT diet with Devazepide (DVZ) 166.2 _+ 3.47; LCT diet with vehicle 165.8 _+ 3.09; LCT diet with DVZ 166.0 _+ 2.66. The DVZ, a type A receptor antagonist of CCK, was a gift from Merck Sharp & Dohme Research Laboratories (Hallow, Essex, England).
Diet Preparation The composition of the experimental diets is shown in Table 1. The MCT source (glyceryl tricaprylate, Coconado RK R) used in the present study was donated by Kao Corp., Wakayama, Japan.
METHOD
Subjects and Housing
Measurement of Food and Water Intake
Male Wistar rats (ST strain, 6 weeks of age) were housed in individual wire mesh cages in a constant-temperature room (24°C) with a 12-h (0400-1600) light cycle. They were ranked
In Experiment 1, cumulative food intake was determined every h for the first 12 h, then at 2-h intervals during the subsequent 12 h. Water intake was measured at 12-h intervals.
J Requests for reprints should be addressed to Dr. M. Furuse.
815
816
F U R U S E ET AL. 1.0.
TABLE 1 DIET COMPOSITION Ingredient Corn starch Cellulose Casein DL-Methionine AIN76 Mineral mix (9) AIN76A Vitamin mix (11) Choline bitartrate Corn oil MCT
LCT (g/kg)
MCT + LCT (g/kg)
200 0
500 50 200 3 35 10 2 100 100
MCT (g/kg)
g
0.5.
0 200 0 0
Feeding was started at 1600 h. In Experiment 2, rats were given a choice between MCT and LCT diets, and food intake was measured at 15-min intervals for 1 h (between 1600-1700 h). Each rat was allocated to two feeders: one feeder with the M C T diet and another with the LCT diet. In Experiment 3, DVZ, dissolved in 1% methylcellulose, was intraperitoneally injected to rats at 0 or 1 mg/kg body weight 40 rain before feeding. Food intake was measured at 1, 2, 3, and 6 h after just the dark period.
15
30
45
60
Min a f t e r f e e d i n g
FIG. 2. Cumulative food intake of growing rats given a choice between diets containing medium chain triglyceride (MCT) and long chain triglyceride (LCT). MCT diet (O), LCT diet (O).
Statistical Procedure Data were subjected to one-way (Experiments 1 and 2) and two-way (Experiment 3) analysis of variance (ANOVA) using a commercially available statistical package (10). Differences between means were determined by Student's t-test in Experiment 1. The data were considered significant when p < 0.05. RESULTS
15
Figure 1 indicates the cumulative food intake of rats fed diets containing graded levels of M C T in Experiment 1. Food intake
10"
10
5-
0 HOUR 0 FAT DVZ INTER 0
2
4
6
8
Hours
10
12 14
after
16 18 20
22
24
feeding
FIG. 1. Cumulative food intake of growing rats fed diets containing medium chain triglycefide (MCT), long chain triglyceride (LCT), or both. MCT diet (~), MCT + LCT diet (O), LCT diet (O). *Significantly different (p < 0.05) from the value for the LCT diet at the same time.
1
2
3
6
**
** **
** *
FIG. 3. Cumulative food intake of growing rats fed diets containing medium chain triglyceride (MCT) and long chain triglyceride (LCT) with or without Devazepide (DVZ). MCT diet without DVZ (O), MCT diet with DVZ (Q), LCT diet without DVZ (Z~),and LCT diet with DVZ (A). FAT, dietary fat sources (MCT vs. LCT); DVZ, Devazepide; INTER, interaction; *p < 0.05; **p < 0.01. Vertical bars represent standard errors of means.
MCT AND FEEDING BEHAVIOR
817
was reduced, in a dose-dependent fashion, with the supplementation of dietary MCT as rapidly as 1 h after feeding. No difference was observed in water intake (ml) among the three groups: 12-h: MCT 10.5 + 0.98, MCT + LCT 10.0 + 1.07, LCT 13.5 __.3.32; 24-h: MCT 13.8 _+ 1.98, MCT + LCT 13.2 + 0.88, LCT 16.1 __- 3.50. Changes in the cumulative food intake of rats given a choice between MCT and LCT diets are shown in Fig. 2. There were no differences in food intake between the two diets. Figure 3 gives the dietary fat source and DVZ on the cumulative food intake. After 2 h of feeding, food intake was significantly enhanced by DVZ. Dietary MCT significantly decreased food intake after 3 h, compared with dietary LCT. No significant interaction was detected during the experimental period. DISCUSSION Medium chain triglyceride is an interesting triglyceride, because its nutritional characteristics are very different from LCT. For instance, MCT can be easily hydrolyzed and absorbed from the intestine in rats (7). The path for the transport of medium chain fatty acids (MCFAs) in the rat is different from that of long chain fatty acids (LCFAs), since the former is transported into the portal vein and lymph and the latter entirely in the lymph (1). After transport to the liver, MCFAs are oxidized quickly and are not incorporated in the lipid ester moieties of lipoproteins (8). Nevertheless, the effect of MCT on feeding behavior has not been investigated precisely.
Recently, Douglas et al. (2) reported that MCT was the most powerful stimulator of CCK secretion in rats; CCK has been suggested to be a satiety hormone (5), because exogenous CCK has been shown to reduce meal size in several mammals (46,12). According to Weller et al. (13), endogenous CCK also plays a significant role in feeding behavior. Chicks fed a diet containing 20% of MCT showed a reduction in food intake over 10 days (3) and drastically enhanced plasma CCK levels (Mabayo, Furuse, Yang, and Okumura, unpublished data), compared with animals given diets containing LCT. In the present study, therefore, feeding behavior of rats was investigated for a short term. As expected, the result clearly showed that food intake of rats was rapidly reduced by dietary MCT in a dose-dependent fashion. This reduction in food intake might be caused by enhanced plasma CCK. However, the possibility that the palatability of MCT was low might be present, because MCFAs such as caproic, caprylic, capric and lauric acids have a poor odor. The palatability of MCT was, therefore, investigated in Experiment 2, but no difference was detected compared with LCT. The reduced food intake due to dietary MCT observed in Experiment 1 could be considered to be induced by satiety signals such as CCK, because CCK was the powerful stimulator of CCK secretion (2). In Experiment 3, therefore, the effect of endogenous CCK was blocked by DVZ. Food intake in both the MCT and LCT groups was improved by DVZ, although the difference in food intake between the two diets was still present. Further mechanisms remain to be investigated. It is concluded that the satiety, but not the palatability, is affected by carbon chain length in dietary triglyceride sources, particularly being a strong effect in MCT.
REFERENCES 1. Bloom, B.; Chaikoff, I. L.; Reinhardt, W. O. Intestinal lymph as pathway for transport of absorbed fatty acids of different chain lengths. Am. J. Physiol. 166:451-455; 1951. 2. Douglas, B. R.; Jansen, J. B. M. J.; de Jong, A. J. L.; Lamers, C. B. H. W. Effect of varioustriglycerideson plasma cholecystokinin levels in rats. J. Nutr. 120:686-690; 1990, 3. Furuse,M.; Mabayo, R. T.; Kita, K.; Okumura, J. Effect of dietary medium chain triglyceride on protein and energy utilization in growing chicks. Br. Poult, Sci. 33:49-57; 1992. 4, Gibbs, J.; Falasco, J. D.; McHugh, G. P. Cholecystokinin-decreased food intake in rhesus monkeys. Am. J. Physiol. 230:15-18; 1976. 5. Gibbs, J.; Young, R. C.; Smith, G. P. Cholecystokinin decreases food intake in rats. J. Comp. Physiol. Psychol. 84:488-495; 1973. 6. Glick,Z.; Thomas, D. W.; Mayer, J. Absence of effect of injections of the intestinal hormones secretion and cholecystokinin-pancreozymin upon feedingbehaviour. Physiol. Behav. 6:5-8; 1971.
7. Greenberger, N. J.; Rodgers, J. B.; lsselbacher, K. J. Absorption of medium and long chain triglycerides:Factors influencing their hydrolysis and transport. J. Clin. Invest. 45:217-227; 1966. 8. Hashim, S. A.; Tantibhedyangkul, P. MCT in early life: Effects on growth of adipose tissue. Lipids 22:429-434; 1987. 9. Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J. Nutr. 107:1340-1348; 1977. 10. SAS Institute, Inc. SAS user's guide: Statistics. Cary, NC: SAS Institute Inc.; 1985. 11. Second report of the ad hoc committee on standards for nutritional studies. J. Nutr. 110:1726; 1980. 12. Sturdevant, R. A. I_.;Goetz, H. Cholecystokininboth stimulate and inhibit human food intake. Nature 261:713-715; 1976. 13. Weller, A.; Smith, G. P.; Gibbs, J. Endogenous cholecystokinin reduces feeding in young rats. Science 247:1589-1591 ; 1990.
0031-9384/92$5.00 + .00 Copyright© 1992PergamonPressLtd.
Printed in the USA.
BRIEF COMMUNICATION
Feeding Behavior in Rats Fed Diets Containing Medium Chain Triglyceride M I T S U H I R O F U R U S E , l Y A N G - H O C H O I , R E M E D I O S T. M A B A Y O A N D J U N - I C H I O K U M U R A
Laboratory of Animal Nutrition, School of Agriculture, Nagoya University, Nagoya 464-01, Japan Received 26 August 1991 FURUSE, M., Y.-H. CHOI, R. T, MABAYO AND J.-I. OKUMURA. Feedingbehavior in ratsfed diets containing medium chain triglyceride. PHYS1OL BEHAV 52(4) 815-817, 1992.--The effect of dietary medium chain triglyceride(MCT) on shortterm food intake was compared with the effect of long chain triglyceride(LCT) in rats. Corn oil and glyceryltricaprylate were used as LCT and MCT sources, respectively. Rats were given diets containing 200 g MCT/kg diet (MCT diet), 100 g MCT + 100 g LCT/kg diet (ML diet), or 200 g LCT/kg diet (LCT diet) in Experiment 1. Cumulative food intake was determined every h for the first 12 h, then at 2-h intervals thereafter during the subsequent 12 h. As early as 1 h after feeding, cumulative food intake significantlydecreased in MCT-fedanimals in a dose-dependent fashion. In Experiment 2, rats were given a choice between MCT and LCT diets for 1 h to confirm whether or not the palatability of diets was influenced by dietary fat sources. There was no difference in food intake between the two diets. In Experiment 3, the responsibilityof endogenous cholecystokinin(CCK) for the difference in food intake between the two diets was investigated for 6 h by using a CCK-A receptor antagonist, Devazepide (DVZ, 1 mg/kg b. wt.). Food intake in the MCT diet and also in the LCT diet was improved by DVZ. it is concluded that the satiety, but not the palatability, is affected by carbon chain length in dietary triglyceridesources, although the responsibilityof endogenous CCK is very small. Medium chain triglyceride
Food intake
Rat
Devazepide
MEDIUM chain triglyceride (MCT), in which fatty acids have carbon chain length from 6 to 12, is different from long chain triglyceride (LCT) in nutritional characteristics. For instance, cholecystokinin (CCK) secretion in rats was drastically enhanced by dietary MCT compared with dietary LCT (2). Cholecystokinin is known to be a satiety hormone (5). Recently, Weiler et al. (13) confirmed that endogenous CCK also played a significant role in feeding behavior. In fact, dietary MCT decreased food intake in chicks (3) and plasma CCK level was enhanced by dietary MCT vs. dietary LCT (Mabayo, Furuse, Yang, and Okumura, unpublished data). Whether or not feeding behavior in rats is affected by dietary MCT has not been investigated in a short-term period. Therefore, the present study was conducted to investigate food intake of rats given diets with two different MCT levels. Furthermore, the palatability and the responsibility of endogenous CCK were also determined.
by weight and divided into experimental groups in order to distribute body weight as uniformly as possible. Body weights (g) were: MCT group 174.5 (mean) _+ 3.52 (SEM); MCT + LCT group 174.3 _+ 3.33; LCT group 174.5 _+ 3.38 in Experiment 1. The numbers of replicates were four per diet in Experiment I. In Experiment 2, five rats (body weight, 169.4 _+ 4.34 g) were used for a choice feeding. In Experiment 3 body weights (g) were: MCT diet with vehicle 164.6 _+ 5.56; MCT diet with Devazepide (DVZ) 166.2 _+ 3.47; LCT diet with vehicle 165.8 _+ 3.09; LCT diet with DVZ 166.0 _+ 2.66. The DVZ, a type A receptor antagonist of CCK, was a gift from Merck Sharp & Dohme Research Laboratories (Hallow, Essex, England).
Diet Preparation The composition of the experimental diets is shown in Table 1. The MCT source (glyceryl tricaprylate, Coconado RK R) used in the present study was donated by Kao Corp., Wakayama, Japan.
METHOD
Subjects and Housing
Measurement of Food and Water Intake
Male Wistar rats (ST strain, 6 weeks of age) were housed in individual wire mesh cages in a constant-temperature room (24°C) with a 12-h (0400-1600) light cycle. They were ranked
In Experiment 1, cumulative food intake was determined every h for the first 12 h, then at 2-h intervals during the subsequent 12 h. Water intake was measured at 12-h intervals.
J Requests for reprints should be addressed to Dr. M. Furuse.
815
816
F U R U S E ET AL. 1.0.
TABLE 1 DIET COMPOSITION Ingredient Corn starch Cellulose Casein DL-Methionine AIN76 Mineral mix (9) AIN76A Vitamin mix (11) Choline bitartrate Corn oil MCT
LCT (g/kg)
MCT + LCT (g/kg)
200 0
500 50 200 3 35 10 2 100 100
MCT (g/kg)
g
0.5.
0 200 0 0
Feeding was started at 1600 h. In Experiment 2, rats were given a choice between MCT and LCT diets, and food intake was measured at 15-min intervals for 1 h (between 1600-1700 h). Each rat was allocated to two feeders: one feeder with the M C T diet and another with the LCT diet. In Experiment 3, DVZ, dissolved in 1% methylcellulose, was intraperitoneally injected to rats at 0 or 1 mg/kg body weight 40 rain before feeding. Food intake was measured at 1, 2, 3, and 6 h after just the dark period.
15
30
45
60
Min a f t e r f e e d i n g
FIG. 2. Cumulative food intake of growing rats given a choice between diets containing medium chain triglyceride (MCT) and long chain triglyceride (LCT). MCT diet (O), LCT diet (O).
Statistical Procedure Data were subjected to one-way (Experiments 1 and 2) and two-way (Experiment 3) analysis of variance (ANOVA) using a commercially available statistical package (10). Differences between means were determined by Student's t-test in Experiment 1. The data were considered significant when p < 0.05. RESULTS
15
Figure 1 indicates the cumulative food intake of rats fed diets containing graded levels of M C T in Experiment 1. Food intake
10"
10
5-
0 HOUR 0 FAT DVZ INTER 0
2
4
6
8
Hours
10
12 14
after
16 18 20
22
24
feeding
FIG. 1. Cumulative food intake of growing rats fed diets containing medium chain triglycefide (MCT), long chain triglyceride (LCT), or both. MCT diet (~), MCT + LCT diet (O), LCT diet (O). *Significantly different (p < 0.05) from the value for the LCT diet at the same time.
1
2
3
6
**
** **
** *
FIG. 3. Cumulative food intake of growing rats fed diets containing medium chain triglyceride (MCT) and long chain triglyceride (LCT) with or without Devazepide (DVZ). MCT diet without DVZ (O), MCT diet with DVZ (Q), LCT diet without DVZ (Z~),and LCT diet with DVZ (A). FAT, dietary fat sources (MCT vs. LCT); DVZ, Devazepide; INTER, interaction; *p < 0.05; **p < 0.01. Vertical bars represent standard errors of means.
MCT AND FEEDING BEHAVIOR
817
was reduced, in a dose-dependent fashion, with the supplementation of dietary MCT as rapidly as 1 h after feeding. No difference was observed in water intake (ml) among the three groups: 12-h: MCT 10.5 + 0.98, MCT + LCT 10.0 + 1.07, LCT 13.5 __.3.32; 24-h: MCT 13.8 _+ 1.98, MCT + LCT 13.2 + 0.88, LCT 16.1 __- 3.50. Changes in the cumulative food intake of rats given a choice between MCT and LCT diets are shown in Fig. 2. There were no differences in food intake between the two diets. Figure 3 gives the dietary fat source and DVZ on the cumulative food intake. After 2 h of feeding, food intake was significantly enhanced by DVZ. Dietary MCT significantly decreased food intake after 3 h, compared with dietary LCT. No significant interaction was detected during the experimental period. DISCUSSION Medium chain triglyceride is an interesting triglyceride, because its nutritional characteristics are very different from LCT. For instance, MCT can be easily hydrolyzed and absorbed from the intestine in rats (7). The path for the transport of medium chain fatty acids (MCFAs) in the rat is different from that of long chain fatty acids (LCFAs), since the former is transported into the portal vein and lymph and the latter entirely in the lymph (1). After transport to the liver, MCFAs are oxidized quickly and are not incorporated in the lipid ester moieties of lipoproteins (8). Nevertheless, the effect of MCT on feeding behavior has not been investigated precisely.
Recently, Douglas et al. (2) reported that MCT was the most powerful stimulator of CCK secretion in rats; CCK has been suggested to be a satiety hormone (5), because exogenous CCK has been shown to reduce meal size in several mammals (46,12). According to Weller et al. (13), endogenous CCK also plays a significant role in feeding behavior. Chicks fed a diet containing 20% of MCT showed a reduction in food intake over 10 days (3) and drastically enhanced plasma CCK levels (Mabayo, Furuse, Yang, and Okumura, unpublished data), compared with animals given diets containing LCT. In the present study, therefore, feeding behavior of rats was investigated for a short term. As expected, the result clearly showed that food intake of rats was rapidly reduced by dietary MCT in a dose-dependent fashion. This reduction in food intake might be caused by enhanced plasma CCK. However, the possibility that the palatability of MCT was low might be present, because MCFAs such as caproic, caprylic, capric and lauric acids have a poor odor. The palatability of MCT was, therefore, investigated in Experiment 2, but no difference was detected compared with LCT. The reduced food intake due to dietary MCT observed in Experiment 1 could be considered to be induced by satiety signals such as CCK, because CCK was the powerful stimulator of CCK secretion (2). In Experiment 3, therefore, the effect of endogenous CCK was blocked by DVZ. Food intake in both the MCT and LCT groups was improved by DVZ, although the difference in food intake between the two diets was still present. Further mechanisms remain to be investigated. It is concluded that the satiety, but not the palatability, is affected by carbon chain length in dietary triglyceride sources, particularly being a strong effect in MCT.
REFERENCES 1. Bloom, B.; Chaikoff, I. L.; Reinhardt, W. O. Intestinal lymph as pathway for transport of absorbed fatty acids of different chain lengths. Am. J. Physiol. 166:451-455; 1951. 2. Douglas, B. R.; Jansen, J. B. M. J.; de Jong, A. J. L.; Lamers, C. B. H. W. Effect of varioustriglycerideson plasma cholecystokinin levels in rats. J. Nutr. 120:686-690; 1990, 3. Furuse,M.; Mabayo, R. T.; Kita, K.; Okumura, J. Effect of dietary medium chain triglyceride on protein and energy utilization in growing chicks. Br. Poult, Sci. 33:49-57; 1992. 4, Gibbs, J.; Falasco, J. D.; McHugh, G. P. Cholecystokinin-decreased food intake in rhesus monkeys. Am. J. Physiol. 230:15-18; 1976. 5. Gibbs, J.; Young, R. C.; Smith, G. P. Cholecystokinin decreases food intake in rats. J. Comp. Physiol. Psychol. 84:488-495; 1973. 6. Glick,Z.; Thomas, D. W.; Mayer, J. Absence of effect of injections of the intestinal hormones secretion and cholecystokinin-pancreozymin upon feedingbehaviour. Physiol. Behav. 6:5-8; 1971.
7. Greenberger, N. J.; Rodgers, J. B.; lsselbacher, K. J. Absorption of medium and long chain triglycerides:Factors influencing their hydrolysis and transport. J. Clin. Invest. 45:217-227; 1966. 8. Hashim, S. A.; Tantibhedyangkul, P. MCT in early life: Effects on growth of adipose tissue. Lipids 22:429-434; 1987. 9. Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J. Nutr. 107:1340-1348; 1977. 10. SAS Institute, Inc. SAS user's guide: Statistics. Cary, NC: SAS Institute Inc.; 1985. 11. Second report of the ad hoc committee on standards for nutritional studies. J. Nutr. 110:1726; 1980. 12. Sturdevant, R. A. I_.;Goetz, H. Cholecystokininboth stimulate and inhibit human food intake. Nature 261:713-715; 1976. 13. Weller, A.; Smith, G. P.; Gibbs, J. Endogenous cholecystokinin reduces feeding in young rats. Science 247:1589-1591 ; 1990.
