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Long-term optional ingestion of corn oil induces excessive caloric intake and obesity in mice
BASIC NUTRITIONAL INVESTIGATION
Long-Term Optional Ingestion of Corn Oil Induces Excessive Caloric Intake and Obesity in Mice Masami Takeda, MSc, Masahiro Imaizumi, PhD, Shoko Sawano, BSc, Yasuko Manabe, PhD, and Tohru Fushiki, PhD From the Laboratory of Nutrition Chemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan Corn oil is well tolerated by mice but tolerance may decrease with excessive ingestion. In the present study, we compared the effects of optional ingestion of excessive corn oil with ingestion of water (control) or a 20% sucrose solution in mice. During the entire study, mice consistently ingested 100% corn oil and incrementally ingested 20% sucrose. Food intake in the corn-oil group was approximately constant but that in the sucrose group was slightly decreased. Body-weight gains in the corn-oil group were higher than those in the control and sucrose groups. At the end of the study, hepatic hypertrophy and fatty liver were present, especially in the corn-oil group, and the visceral fat of mice fed corn oil increased significantly compared with the other two groups. These results suggest that mice, when given a choice, will continue to overeat corn oil over the long term, inducing excessive caloric intake and obesity. Nutrition 2001;17: 117–120. ©Elsevier Science Inc. 2001 Key words: corn oil, hyperphagia, obesity, mice, chronic intake, diet
INTRODUCTION High-fat foods such as those sold in cafeterias and supermarkets are often preferred by most people. Intake of highly palatable oily or fatty foods often induces excessive caloric consumption and obesity as risk factors from lifestyle-related diseases in humans.1– 6 Some researchers have reported that the smell, texture, and postingestive effects of fat contribute its preference in rats.7–12 We recently showed in mice that the preference for oils was induced by fat stimulating the oral cavity but not by postingestive effects.13,14 However, there have been no studies reporting on whether long-term ingestion of oils or fats makes animals maintain this preference. Therefore, we investigated the trend of palatability and ingestion during and after long-term feeding of oils or fats in mice. In several studies, rats selected and consumed high-fat foods from optional diets15 and cafeteria-style diets containing high levels of fat,16,17 resulting in excessive caloric intake and obesity from long-term ingestion of fats. Several studies have addressed the issue of excessive caloric intake and obesity induced by longterm ingestion of dietary fat. Warwick reported that the postingestive effects of fats enhance daily caloric intake because fat produces less satiety and less suppression of the intake in rats.18,19 Rogers and Blundell reported that food palatability and variety were important in excessive caloric intake and that obesity caused by overconsumption could be induced without increasing the fat content or caloric density of the diet.16 Although fats and oils themselves are highly palatable in rodents, there are few reports investigating this palatability in relation to excessive caloric intake
This research was supported by a grant from the Japanese Society for the Promotion of Science (JSPS-RFTF97L00906). Correspondence to: Masahiro Imaizumi, PhD, Laboratory of Nutrition Chemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. E-mail: [email protected] Date accepted: August 21, 2000. Nutrition 17:117–120, 2001 ©Elsevier Science Inc., 2001. Printed in the United States. All rights reserved.
and obesity. To study this question, we provided corn oil ad libitum over a long term to mice and let the mice choose whether or not to eat it to observe whether optional ingestion of corn oil induces excessive caloric intake and obesity in mice. Because our previous study showed that mice also preferred sucrose solution,13 we used the same sucrose solution as a highly palatable non-fat control and compared the effects with those corn-oil intake. Preference for sucrose solution over vehicle in mice in the two-bottle choice test increased in a concentrationdependent manner, but this preference seemed to reach a plateau at concentrations ⬎5%.13 The highly viscous solution was difficult to use in a bottle, so we used 20% sucrose solution in the present study. We report the effects of long-term ingestion of corn oil as an optional diet for mice; we also report on intake, regular food intake, body-weight gains, and accumulations of visceral fat.
MATERIALS AND METHODS Animals Male ddY mice (Japan SLC, Inc., Hamamatsu, Japan) were purchased at age 5 wk. The animals were maintained under controlled conditions, a 12-h light (from 6 AM) and 12-h dark cycle, and a constant temperature of 23 ⫾ 3°C. Food and water were freely available in the home cages. Procedure Fifty-four mice in 18 cages (n ⫽ 3/cage) were assigned to three groups and all had free access to water and rat chow (MF; Oriental Yeast Company, Ltd., Chiba, Japan). The control group drank only water; the sucrose group drank a 20% sucrose solution (Nacarai Tesqu Company, Inc., Kyoto, Japan), and the corn-oil group drank 100% corn oil (Ajinomoto Company, Inc., Tokyo, Japan) for 42 d. Food and sample intakes per cage and body weights were measured daily at about 10 AM except on holidays. The corn oil provided 9.21 kcal/g, the 20% sucrose solution provided 0.77 kcal/g, and the regular chow provided 3.57 kcal/g in estimation. After measuring body weights and intake of vehicles and chow on 0899-9007/01/$20.00 PII S0899-9007(00)00513-X
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day 42, the mice were killed and dissected. Organ weights and visceral fat were measured, and fatty liver was determined by observing its appearance. Statistical Analysis Measurements of body-weight gains and intake of vehicle and chow were averaged per mouse every Monday and Friday. Differences between the starting weight and the final weight were statistically evaluated by the paired t test. The one-way analysis of variance and post hoc Tukey test were used to analyze bodyweight gains, intakes of vehicle, chow, and total calories, and weights of organs and visceral fat; the 2 test was used to analyze the number of fatty livers.
RESULTS Mice consistently consumed 100% corn oil and 20% sucrose for 42 d. Intakes of corn oil and chow in the corn-oil group largely remained the same throughout the study (Figs. 1A and 1B). Intake of 20% sucrose solution in the sucrose group gradually increased, and intake on day 42 was significantly different from that on day 1 (Fig. 1A). Chow intake decreased slightly during the study (Fig. 1B), and the intakes on days 39 and 42 were significantly lower than that on day 4 (both Ps ⬍ 0.01, Tukey test). Total caloric ingestion from chow and vehicles was higher in the corn-oil group than the other two groups (Fig. 1C). Final weights were significantly different from starting weights in all groups (P ⬍ 0.001, paired t test). Body-weight gains in the corn-oil group were significantly higher than those in the control group from day 4 and the sucrose group from day 8 (Fig. 2). Body-weight gains in the sucrose group were significantly higher than those in the control group from day 8 (Fig. 2). On day 42, hearts, lungs, livers, spleens, kidneys, testes, perinephric fat, epididymal fat, and mesenteric fat were dissected out. Although the weights of heart, lung, liver, spleen, kidneys, and testes did not differ significantly across groups, significant differences were observed in liver weights between the control and corn-oil groups (P ⬍ 0.01) and the sucrose group (P ⬍ 0.05, Tukey test; Fig. 3). The weights of perinephric fat, epididymal fat, and mesenteric fat differed significantly across groups (Fig. 3). Moreover, fatty livers were observed in all mice in the corn-oil group, eight in the sucrose group, and one in the control group (P ⬍ 0.0001, 2 test).
DISCUSSION The present results show that mice continued to prefer corn oil and consequently developed excessive caloric intake and obesity. The mice in the present study were given corn oil or sucrose solution as an optional supplement to regular rat chow. In the study by Warwick, the postingestive effects of a high-fat diet promoted larger meal size and increased daily caloric intake due to decreased postprandial satiety per calorie than a high-carbohydrate diet in humans and rats.19 Ramirez and Friedman showed that excessive caloric intake in rats was induced by the consumption of highcalorie diets that included high levels of both fat and carbohydrate.20 A previous study reported that the availability of many food varieties was an important factor in the development of excessive caloric intake and obesity because rats fed a variety of foods simultaneously were more hyperphagic and gained significantly more body weight and fat.17 In the present study, the amount of corn-oil intake was maintained during the entire study, indicating that the high palatability of the oil contributes to the production of excessive caloric intake and obesity. We previously reported the effects of excessive corn-oil intake on the preference for corn oil versus sucrose in mice.13 In this report, excessive
FIG. 1. Effects of excessive calories on (A) corn oil and sucrose (samples) intake, (B) food (chow) intake, and (C) total caloric intake. Mice were given 100% corn oil, 20% sucrose, or water (control) ad libitum for 42 d. Intake amounts of (A) corn oil or sucrose and (B) chow were measured almost daily during the study and were averaged every Monday and Friday. Total caloric intake (C) was calculated from calories in 100% corn oil, 20% sucrose, and chow and multiplied by each amount. Symbols and error bars represent the mean ⫾ SE of 6 cages (18 mice per group, 3 per cage). Circles, control group; squares, sucrose group; triangles, corn-oil group. (A) Time-dependent effects between data obtained on day 1 and data obtained on days 2 to 42 were analyzed with the Tukey test: aP ⬍ 0.05, b P ⬍ 0.01 versus day 1. Statistical significance across groups at each 3- or 4-d block was also analyzed with the Tukey test: (B) *P ⬍ 0.01 versus the corn-oil and sucrose groups, #P ⬍ 0.05 versus the sucrose group; (C) aP ⬍ 0.05, bP ⬍ 0.01 versus the control group, cP ⬍ 0.01 versus the sucrose group.
corn-oil intake did not greatly affect the preference of mice for lower concentrations (2, 5, and 10%) of corn oil as opposed to a preference for sucrose. The preference for 2 and 5% sucrose in the sucrose group decreased after chronic intake. Therefore, this preference for fat may be inherent and thus may explain long-term excessive caloric intake of corn oil in mice. Corn oil is high in calories compared with 20% sucrose solution and regular chow. Because total caloric intake was greater in the corn-oil group than in the other two groups, mice in the corn-oil group had the greatest increases in body weight and accumulation of visceral fat. In the sucrose group, sucrose intake
Nutrition Volume 17, Number 2, 2001
FIG. 2. Effects of excessive long-term intake of corn oil and sucrose on body-weight gain. Mice were given 100% corn oil, 20% sucrose, or water (control) ad libitum for 42 d. Body weights were measured almost daily during the study and averaged every Monday and Friday, and then bodyweight gain was calculated. Symbols and error bars represent the mean ⫾ SE of 18 mice per group. Circles, control group; squares, sucrose group; triangles, corn-oil group. Statistical significance across groups at each 3- or 4-d block was analyzed with the Tukey test: aP ⬍ 0.01 versus the control group, bP ⬍ 0.05 and cP ⬍ 0.01 versus the sucrose group.
gradually increased but chow intake gradually decreased, and total caloric intake was approximately maintained at the lower level in comparison with the corn-oil group. Thus, body-weight gain, accumulation of visceral fat, and hepatic hypertrophy were not as great. In accordance with our results, Rattigan and Clark reported that the optional sucrose solution decreased solid-food intake, increased body weight, and increased the body fat index without significant increases in total caloric intake of a low-fat, highcarbohydrate diet.21 In the present study, fatty livers were observed in all mice in the corn-oil group and in half the mice in the sucrose group. We determined fatty liver only by observing a color that was clearly different from that of normal liver; we did not use biochemical analysis. Therefore, only malignant cases of fatty liver may have been noted. Further studies are needed to clarify the severity of fatty liver with the use of biochemical measurements. Fatty liver has been observed with excessive intake of alcohol22,23 and has been reported in rats on a low-protein diet due to decreased synthesis of apolipoprotein and albumin in the liver.24 –27 In the
FIG. 3. Effects of excessive long-term intake of corn oil and sucrose on accumulation of visceral fat and liver weight. Mice were given 100% corn oil, 20% sucrose, or water (control) ad libitum for 42 d. On day 42, mice were killed and the following tissues were dissected out and weighed: perinephric fat, epididymal fat, mesenteric fat, and liver. Bars and error bars represent the mean ⫾ SE of 18 mice per group. Statistical significance across groups was analyzed with the Tukey test: aP ⬍ 0.05 and bP ⬍ 0.01 versus the control group, cP ⬍ 0.05 and dP ⬍ 0.01 versus the sucrose group.
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present study, the proportion of calories from protein in the control group was calculated as approximately 28.1%, whereas the proportions in the corn-oil and the sucrose groups were approximately 12.5% and 15.5%, respectively. Therefore, the relatively low amount of protein ingested by the corn-oil and sucrose groups may have contributed to the larger number of fatty livers. Mice in the corn-oil and sucrose groups also ingested relatively low levels of vitamins and minerals compared with mice in the control group, even though the rat chow contained adequate amounts of these nutrients, suggesting that corn oil and sucrose reduced ingestion of nutrients other than protein. Moreover, the larger number of fatty livers in the sucrose group and especially the corn-oil group suggest that these mice ingested excessive calories and accumulated visceral fat. A human study reported that excess dietary fats rather than excess dietary carbohydrates lead to greater fat accumulation and that the greatest difference is observed early in the overfeeding period.28 In the present study, body-weight gain and visceral-fat accumulation were significantly higher in the corn-oil group than in the sucrose group, although the mice in the corn-oil group consumed more calories. The product of body-weight gain and visceral-fat accumulation divided by the number of calories consumed was higher in the corn-oil group than in the sucrose group, although the difference was not statistically significant (data not shown). Excess dietary fats rather than excess dietary carbohydrates in mice may also lead to greater fat accumulation. Conditioned flavor preferences based on the postingestive effects of fat intake may contribute to a preference for high-fat foods in children29 and as a consequence may cause excessive caloric intake and obesity in adulthood.
SUMMARY The present study showed that the palatability of corn oil was so strong that mice continued to ingest excessive calories, became obese, and developed fatty livers when they ingested corn oil as the optional diet.
REFERENCES 1. Koop G. Surgeon General takes aim at saturated fats. Science 1998;241:651 2. Ascherio A. New directions in dietary studies of coronary heart disease. J Nutr 1995;125:647S 3. Lichtenstein AH, Kennedy E, Barrier P, et al. Dietary fat consumption and health. Nutr Rev 1998;56:S3 4. Popkin BM, Doak CM. The obesity epidemic is a worldwide phenomenon. Nutr Rev 1998;56:106 5. Mela DJ. Understanding fat preference and consumption: applications of behavioral sciences to a nutritional problem. Proc Nutr Soc 1995;54:453 6. West DB, York B. Dietary fat, genetic predisposition, and obesity: lessons from animal models. Am J Clin Nutr 1998;67:505S 7. Elizalde G, Sclafani A. Fat appetite in rats: flavor preferences conditioned by nutritive and non-nutritive oil emulsions. Appetite 1990;15:189 8. Naim M, Brand JG, Kare MR. The preference–aversion behavior of rats for nutritionally-controlled diets containing oil or fat. Physiol Behav 1987;39:285 9. Ramirez I. Chemosensory similarities among oils: does viscosity play a role? Chem Senses 1994;19:155 10. Drewnowski A. Why do we like fat? J Am Diet Assoc 1997;97:S58 11. Drewnowski A, Schwartz M. Invisible fats: sensory assessment of sugar/fat mixtures. Appetite 1990;14:203 12. Ramirez I. Role of olfaction in starch and oil preference. Am J Physiol 1993; 265:R1404 13. Takeda M, Imaizumi M, Fushiki T. Preference for vegetable oils in the two-bottle choice test in mice. Life Sci 2000;67:197 14. Imaizumi M, Takeda M, Fushiki T. Effects of oil intake in the conditioned place preference test in mice. Brain Res 2000;870:150 15. Lucas F, Ackroff K, Sclafani A. Dietary fat-induced hyperphagia in rats as a function of fat type and physical form. Physiol Behav 1989;45:937
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16. Rogers PJ, Blundell JE. Meal patterns and food selection during the development of obesity in rats fed a cafeteria diet. Neurosci Biobehav Rev 1984;8:441 17. Rolls BJ, Van Duijvenvoorde PM, Rowe EA. Variety in the diet enhances intake in a meal and contributes to the development of obesity in the rat. Physiol Behav 1983;31:21 18. Warwick ZS, Weingarten HP. Determinants of high-fat diet hyperphagia: experimental dissection of orosensory and postingestive effects. Am J Physiol 1995; 269:R30 19. Warwick ZS. Probing the causes of high-fat diet hyperphagia: a mechanistic and behavioral dissection. Neurosci Biobehav Rev 1996;20:155 20. Ramirez I, Friedman M. Dietary hyperphagia in rats: role of fat, carbohydrate, and energy content. Physiol Behav 1990;47:1157 21. Rattigan S, Clark MG. Effect of sucrose solution drinking option on the development of obesity in rats. J Nutr 1984;144:1971 22. Lieber CS. Hepatic and metabolic effects of alcohol. Gastroenterology 1966;50:119 23. Lieber CS, Spritz N, DeCarli LM. Role of dietary, adipose, and endogenously
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24. 25. 26. 27.
28. 29.
synthesized fatty acids in the pathogenesis of the alcoholic fatty liver. J Clin Invest 1966;45:51 Seakins A, Waterlow JC. Effect of a low-protein diet on the incorporation of amino acids into rat serum lipoproteins. Biochem J 1972;129:793 Sato M, Nagao K, Sakono M, et al. Low protein diets posttranscriptionally repress apolipoprotein B expression in rat liver. J Nutr Biochem 1996;7:381 Flores H, Sierralta W, Monckeberg F. Triglyceride transport in protein-depleted rats. J Nutr 1970;100:375 Sakuma K, Ohyama T, Sogawa K, Fujii-Kuriyama Y, Matsumura Y. Low protein– high energy diet induces repressed transcription of albumin mRNA in rat liver. J Nutr 1987;117:1141 Horton TJ, Drougas H, Brachey A, et al. Fat and carbohydrate overfeeding in humans: different effects of energy storage. Am J Clin Nutr 1995;62:19 Kern DL, McPhee L, Fisher J, Johnson S, Birch LL. The postingestive consequences of fat condition preferences for flavors associated with high dietary fat. Physiol Behav 1993;54:71
Long-Term Optional Ingestion of Corn Oil Induces Excessive Caloric Intake and Obesity in Mice Masami Takeda, MSc, Masahiro Imaizumi, PhD, Shoko Sawano, BSc, Yasuko Manabe, PhD, and Tohru Fushiki, PhD From the Laboratory of Nutrition Chemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan Corn oil is well tolerated by mice but tolerance may decrease with excessive ingestion. In the present study, we compared the effects of optional ingestion of excessive corn oil with ingestion of water (control) or a 20% sucrose solution in mice. During the entire study, mice consistently ingested 100% corn oil and incrementally ingested 20% sucrose. Food intake in the corn-oil group was approximately constant but that in the sucrose group was slightly decreased. Body-weight gains in the corn-oil group were higher than those in the control and sucrose groups. At the end of the study, hepatic hypertrophy and fatty liver were present, especially in the corn-oil group, and the visceral fat of mice fed corn oil increased significantly compared with the other two groups. These results suggest that mice, when given a choice, will continue to overeat corn oil over the long term, inducing excessive caloric intake and obesity. Nutrition 2001;17: 117–120. ©Elsevier Science Inc. 2001 Key words: corn oil, hyperphagia, obesity, mice, chronic intake, diet
INTRODUCTION High-fat foods such as those sold in cafeterias and supermarkets are often preferred by most people. Intake of highly palatable oily or fatty foods often induces excessive caloric consumption and obesity as risk factors from lifestyle-related diseases in humans.1– 6 Some researchers have reported that the smell, texture, and postingestive effects of fat contribute its preference in rats.7–12 We recently showed in mice that the preference for oils was induced by fat stimulating the oral cavity but not by postingestive effects.13,14 However, there have been no studies reporting on whether long-term ingestion of oils or fats makes animals maintain this preference. Therefore, we investigated the trend of palatability and ingestion during and after long-term feeding of oils or fats in mice. In several studies, rats selected and consumed high-fat foods from optional diets15 and cafeteria-style diets containing high levels of fat,16,17 resulting in excessive caloric intake and obesity from long-term ingestion of fats. Several studies have addressed the issue of excessive caloric intake and obesity induced by longterm ingestion of dietary fat. Warwick reported that the postingestive effects of fats enhance daily caloric intake because fat produces less satiety and less suppression of the intake in rats.18,19 Rogers and Blundell reported that food palatability and variety were important in excessive caloric intake and that obesity caused by overconsumption could be induced without increasing the fat content or caloric density of the diet.16 Although fats and oils themselves are highly palatable in rodents, there are few reports investigating this palatability in relation to excessive caloric intake
This research was supported by a grant from the Japanese Society for the Promotion of Science (JSPS-RFTF97L00906). Correspondence to: Masahiro Imaizumi, PhD, Laboratory of Nutrition Chemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. E-mail: [email protected] Date accepted: August 21, 2000. Nutrition 17:117–120, 2001 ©Elsevier Science Inc., 2001. Printed in the United States. All rights reserved.
and obesity. To study this question, we provided corn oil ad libitum over a long term to mice and let the mice choose whether or not to eat it to observe whether optional ingestion of corn oil induces excessive caloric intake and obesity in mice. Because our previous study showed that mice also preferred sucrose solution,13 we used the same sucrose solution as a highly palatable non-fat control and compared the effects with those corn-oil intake. Preference for sucrose solution over vehicle in mice in the two-bottle choice test increased in a concentrationdependent manner, but this preference seemed to reach a plateau at concentrations ⬎5%.13 The highly viscous solution was difficult to use in a bottle, so we used 20% sucrose solution in the present study. We report the effects of long-term ingestion of corn oil as an optional diet for mice; we also report on intake, regular food intake, body-weight gains, and accumulations of visceral fat.
MATERIALS AND METHODS Animals Male ddY mice (Japan SLC, Inc., Hamamatsu, Japan) were purchased at age 5 wk. The animals were maintained under controlled conditions, a 12-h light (from 6 AM) and 12-h dark cycle, and a constant temperature of 23 ⫾ 3°C. Food and water were freely available in the home cages. Procedure Fifty-four mice in 18 cages (n ⫽ 3/cage) were assigned to three groups and all had free access to water and rat chow (MF; Oriental Yeast Company, Ltd., Chiba, Japan). The control group drank only water; the sucrose group drank a 20% sucrose solution (Nacarai Tesqu Company, Inc., Kyoto, Japan), and the corn-oil group drank 100% corn oil (Ajinomoto Company, Inc., Tokyo, Japan) for 42 d. Food and sample intakes per cage and body weights were measured daily at about 10 AM except on holidays. The corn oil provided 9.21 kcal/g, the 20% sucrose solution provided 0.77 kcal/g, and the regular chow provided 3.57 kcal/g in estimation. After measuring body weights and intake of vehicles and chow on 0899-9007/01/$20.00 PII S0899-9007(00)00513-X
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day 42, the mice were killed and dissected. Organ weights and visceral fat were measured, and fatty liver was determined by observing its appearance. Statistical Analysis Measurements of body-weight gains and intake of vehicle and chow were averaged per mouse every Monday and Friday. Differences between the starting weight and the final weight were statistically evaluated by the paired t test. The one-way analysis of variance and post hoc Tukey test were used to analyze bodyweight gains, intakes of vehicle, chow, and total calories, and weights of organs and visceral fat; the 2 test was used to analyze the number of fatty livers.
RESULTS Mice consistently consumed 100% corn oil and 20% sucrose for 42 d. Intakes of corn oil and chow in the corn-oil group largely remained the same throughout the study (Figs. 1A and 1B). Intake of 20% sucrose solution in the sucrose group gradually increased, and intake on day 42 was significantly different from that on day 1 (Fig. 1A). Chow intake decreased slightly during the study (Fig. 1B), and the intakes on days 39 and 42 were significantly lower than that on day 4 (both Ps ⬍ 0.01, Tukey test). Total caloric ingestion from chow and vehicles was higher in the corn-oil group than the other two groups (Fig. 1C). Final weights were significantly different from starting weights in all groups (P ⬍ 0.001, paired t test). Body-weight gains in the corn-oil group were significantly higher than those in the control group from day 4 and the sucrose group from day 8 (Fig. 2). Body-weight gains in the sucrose group were significantly higher than those in the control group from day 8 (Fig. 2). On day 42, hearts, lungs, livers, spleens, kidneys, testes, perinephric fat, epididymal fat, and mesenteric fat were dissected out. Although the weights of heart, lung, liver, spleen, kidneys, and testes did not differ significantly across groups, significant differences were observed in liver weights between the control and corn-oil groups (P ⬍ 0.01) and the sucrose group (P ⬍ 0.05, Tukey test; Fig. 3). The weights of perinephric fat, epididymal fat, and mesenteric fat differed significantly across groups (Fig. 3). Moreover, fatty livers were observed in all mice in the corn-oil group, eight in the sucrose group, and one in the control group (P ⬍ 0.0001, 2 test).
DISCUSSION The present results show that mice continued to prefer corn oil and consequently developed excessive caloric intake and obesity. The mice in the present study were given corn oil or sucrose solution as an optional supplement to regular rat chow. In the study by Warwick, the postingestive effects of a high-fat diet promoted larger meal size and increased daily caloric intake due to decreased postprandial satiety per calorie than a high-carbohydrate diet in humans and rats.19 Ramirez and Friedman showed that excessive caloric intake in rats was induced by the consumption of highcalorie diets that included high levels of both fat and carbohydrate.20 A previous study reported that the availability of many food varieties was an important factor in the development of excessive caloric intake and obesity because rats fed a variety of foods simultaneously were more hyperphagic and gained significantly more body weight and fat.17 In the present study, the amount of corn-oil intake was maintained during the entire study, indicating that the high palatability of the oil contributes to the production of excessive caloric intake and obesity. We previously reported the effects of excessive corn-oil intake on the preference for corn oil versus sucrose in mice.13 In this report, excessive
FIG. 1. Effects of excessive calories on (A) corn oil and sucrose (samples) intake, (B) food (chow) intake, and (C) total caloric intake. Mice were given 100% corn oil, 20% sucrose, or water (control) ad libitum for 42 d. Intake amounts of (A) corn oil or sucrose and (B) chow were measured almost daily during the study and were averaged every Monday and Friday. Total caloric intake (C) was calculated from calories in 100% corn oil, 20% sucrose, and chow and multiplied by each amount. Symbols and error bars represent the mean ⫾ SE of 6 cages (18 mice per group, 3 per cage). Circles, control group; squares, sucrose group; triangles, corn-oil group. (A) Time-dependent effects between data obtained on day 1 and data obtained on days 2 to 42 were analyzed with the Tukey test: aP ⬍ 0.05, b P ⬍ 0.01 versus day 1. Statistical significance across groups at each 3- or 4-d block was also analyzed with the Tukey test: (B) *P ⬍ 0.01 versus the corn-oil and sucrose groups, #P ⬍ 0.05 versus the sucrose group; (C) aP ⬍ 0.05, bP ⬍ 0.01 versus the control group, cP ⬍ 0.01 versus the sucrose group.
corn-oil intake did not greatly affect the preference of mice for lower concentrations (2, 5, and 10%) of corn oil as opposed to a preference for sucrose. The preference for 2 and 5% sucrose in the sucrose group decreased after chronic intake. Therefore, this preference for fat may be inherent and thus may explain long-term excessive caloric intake of corn oil in mice. Corn oil is high in calories compared with 20% sucrose solution and regular chow. Because total caloric intake was greater in the corn-oil group than in the other two groups, mice in the corn-oil group had the greatest increases in body weight and accumulation of visceral fat. In the sucrose group, sucrose intake
Nutrition Volume 17, Number 2, 2001
FIG. 2. Effects of excessive long-term intake of corn oil and sucrose on body-weight gain. Mice were given 100% corn oil, 20% sucrose, or water (control) ad libitum for 42 d. Body weights were measured almost daily during the study and averaged every Monday and Friday, and then bodyweight gain was calculated. Symbols and error bars represent the mean ⫾ SE of 18 mice per group. Circles, control group; squares, sucrose group; triangles, corn-oil group. Statistical significance across groups at each 3- or 4-d block was analyzed with the Tukey test: aP ⬍ 0.01 versus the control group, bP ⬍ 0.05 and cP ⬍ 0.01 versus the sucrose group.
gradually increased but chow intake gradually decreased, and total caloric intake was approximately maintained at the lower level in comparison with the corn-oil group. Thus, body-weight gain, accumulation of visceral fat, and hepatic hypertrophy were not as great. In accordance with our results, Rattigan and Clark reported that the optional sucrose solution decreased solid-food intake, increased body weight, and increased the body fat index without significant increases in total caloric intake of a low-fat, highcarbohydrate diet.21 In the present study, fatty livers were observed in all mice in the corn-oil group and in half the mice in the sucrose group. We determined fatty liver only by observing a color that was clearly different from that of normal liver; we did not use biochemical analysis. Therefore, only malignant cases of fatty liver may have been noted. Further studies are needed to clarify the severity of fatty liver with the use of biochemical measurements. Fatty liver has been observed with excessive intake of alcohol22,23 and has been reported in rats on a low-protein diet due to decreased synthesis of apolipoprotein and albumin in the liver.24 –27 In the
FIG. 3. Effects of excessive long-term intake of corn oil and sucrose on accumulation of visceral fat and liver weight. Mice were given 100% corn oil, 20% sucrose, or water (control) ad libitum for 42 d. On day 42, mice were killed and the following tissues were dissected out and weighed: perinephric fat, epididymal fat, mesenteric fat, and liver. Bars and error bars represent the mean ⫾ SE of 18 mice per group. Statistical significance across groups was analyzed with the Tukey test: aP ⬍ 0.05 and bP ⬍ 0.01 versus the control group, cP ⬍ 0.05 and dP ⬍ 0.01 versus the sucrose group.
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present study, the proportion of calories from protein in the control group was calculated as approximately 28.1%, whereas the proportions in the corn-oil and the sucrose groups were approximately 12.5% and 15.5%, respectively. Therefore, the relatively low amount of protein ingested by the corn-oil and sucrose groups may have contributed to the larger number of fatty livers. Mice in the corn-oil and sucrose groups also ingested relatively low levels of vitamins and minerals compared with mice in the control group, even though the rat chow contained adequate amounts of these nutrients, suggesting that corn oil and sucrose reduced ingestion of nutrients other than protein. Moreover, the larger number of fatty livers in the sucrose group and especially the corn-oil group suggest that these mice ingested excessive calories and accumulated visceral fat. A human study reported that excess dietary fats rather than excess dietary carbohydrates lead to greater fat accumulation and that the greatest difference is observed early in the overfeeding period.28 In the present study, body-weight gain and visceral-fat accumulation were significantly higher in the corn-oil group than in the sucrose group, although the mice in the corn-oil group consumed more calories. The product of body-weight gain and visceral-fat accumulation divided by the number of calories consumed was higher in the corn-oil group than in the sucrose group, although the difference was not statistically significant (data not shown). Excess dietary fats rather than excess dietary carbohydrates in mice may also lead to greater fat accumulation. Conditioned flavor preferences based on the postingestive effects of fat intake may contribute to a preference for high-fat foods in children29 and as a consequence may cause excessive caloric intake and obesity in adulthood.
SUMMARY The present study showed that the palatability of corn oil was so strong that mice continued to ingest excessive calories, became obese, and developed fatty livers when they ingested corn oil as the optional diet.
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