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Mediating effects of waist circumference and BMI on the association between meal frequency and mortality.

OBJECTIVE: To examine the potential indirect effect of meal frequency on mortality via obesity indices. DESIGN: Prospective cohort study. SETTING: Korean Genome and Epidemiology Study. PARTICIPANTS: This cohort study involved 148 438 South Korean adults aged 40 years and older. RESULTS: Meal frequency at the baseline survey was assessed using a validated FFQ. Outcomes included all-cause mortality, cancer mortality and CVD mortality. Cox proportional hazards regression models were employed to examine the relationship between meal frequency and the risk of mortality. Mediation analyses were performed with changes in obesity indices (BMI and weight circumference (WC)) as mediators. In comparison to the three-time group, the once-per-day and four-times-per-day groups had a higher risk for all-cause mortality. The irregular frequency group had a higher risk for CVD mortality. Both once-per-day and four-times-per-day groups exhibited higher risks for cancer mortality. The effect of meal frequency on all-cause mortality was partially mediated by WC. For specific-cause mortality, similar mediation effects were found. CONCLUSIONS: The data suggests that three meals per day have a lower mortality and longer life expectancy compared with other meal frequencies. Increased waist circumference partially mediates this effect. These findings support the implementation of a strategy that addresses meal frequency and weight reduction together.

Humans

The influence of meal frequency on diurnal lipid, glucose and cortisol levels in normal subjects.

Diurnal levels of serum triglyceride, cholesterol, free fatty acids, glucose, and cortisol were measured in four normal persons on a fixed solid 65% carbohydrate diet under steady state conditions in a metabolic unit. Triglyceride levels in all subjects showed similar patterns, which unexpectedly did not bear a simple relation to meal frequency or distribution. With three equivalent meals per day at 09.00, 12.00 and 17.00 hours, 'fasting' triglyceride levels increased by about 0.3 g/l from a minimum value between 03.00 and 05.00 hours in the morning till before breakfast. After breakfast there was a continued rise till about 15.00 hours and then a overall fall in spite of the meal at 17.00 hours. Isocaloric change to eight equivalent meals, consumed between 09.00 and 23.00 hours, resulted in a similar although slightly more even triglyceride pattern. On eight equivalent meals, spaced evenly over the entire 24 h period, a different pattern was found with lower triglyceride values at daytime than at night. Increase in meal frequency did not result in a lowering of mean diurnal triglyceride levels. The cholesterol pattern followed the triglyceride pattern most clearly in subjects with high triglyceride levels. Glucose showed the expected postprandial increments. Cortisol rhythm did not change on varying meal frequency.

Adult

Influence of meal frequency on diurnal lipid, glucose and insulin levels in normal subjects on a high fat diet; comparison with data obtained on a high carbohydrate diet.

Diurnal levels of serum triglyceride (TG) were measured in six normal persons consuming a fixed solid 65% fat diet under steady state conditions in a metabolic unit. The food was divided into either three or eight similar portions, differently spaced over the day and night. The diurnal TG-profiles on this diet were practically identical to those found under comparable conditions on a 65% carbohydrate diet [1]. Mean diurnal TG values did not significantly differ with varying meal frequency. Free fatty acid levels, however, were significantly higher on a high fat diet. Post-prandial glucose and insulin reponses did not significantly differ whether a high fat diet or a high carbohydrate diet was consumed. We conclude that the composition of the diet is of little importance in determining diurnal TG patterns when the diet consists of normal food stuffs, but that these patterns are dependent on meal frequency and distribution.

Blood Glucose

Influence of alterations in meal frequency on lipogenesis and body fat content in the rat.

Rats were allowed to eat only 2 hr per day (meal-fed) or were fed ad libitum (nibbler) for 12 wk; another group of animals was meal-fed for 3 wk and then fed ad libitum (converted I) while the fourth group of rats (converted II) was meal-fed for 3 wk, allowed to nibble for the next 3 wk, meal-fed from the 6th to 9th wk and then returned to ad libitum feeding for the last 3 wk. Body fat gain and food efficiency was increased in converted I rats. The lipogenic capacity of adipose tissue from meal-fed rats was greater than observen meal-fed rats were reverted to ad libitum feeding whereas lipogenic activity increased rapidly when ad libitum fed rats were switched to meal-feeding.

Acetyl-CoA Carboxylase

The influence of dietary fat and meal frequency on lipoprotein lipase and hormone-sensitive lipase in rat adipose tissue.

Activities of NaCl-inactivated lipoprotein lipase (LPL) and protamine-resistant hormone-sensitive lipase (HSL) in adipose tissue, accumulation of carcass fat, and serum triglycerides (TG) were determined in meal-fed (MF) and ad libitum-fed (AD) rats. At each feeding frequency, diets provided total fat as 15 or 30% of calories and polyunsaturated fatty acids (PUFA) as 2.5 or 11% of calories. The average energy intake of MF rats was 67% that of AD rats. Total weight gained by MF rats was only 60% that of the AD rats. Significantly greater activities of LPL, HSL, and LPL:HSL in adipose of MF rats suggested a greater capacity for fat accumulation which was not realized at the limited energy intake. In AD rats, the percentage of body fat was significantly correlated with LPL:HSL and with serum TG, suggesting that the relative enzyme activities and fat deposition may be influenced by the concentration of circulating TG. Mean body fat of rats receiving the 30% fat diet was significantly greater than that of rats fed 15% fat. Both serum TG and adipose LPL activity were significantly reduced when the diet contained high levels of PUFA.

Adipose Tissue

Free-feeding patterns of rats in response to changes in environmental temperature.

Four adult Sprague-Dawley rats (430-450 g), maintained on a 12:12 h dark/light cycle and 15% casein diet, were exposed to cold (5 degrees C) for 77 days and then transferred back to 24 degrees C. Throughout thisperiod, the feeding patterns of the rats were measured with recording balances. Cold exposure caused an immediate reduction in nocturnal meal frequency that remained low during the cold exposure. In contrast, diurnal meal frequency was unaltered. Average nocturnal meal size, which did not significantly increase before 8 days of cold, reached a plateau in 2 wk, whereas the average diurnal meal size did not significantly change until late in the exposure period. "Warm" (24 degrees C) reentry elicited an abrupt increase in nocturnal meal frequency and a reduction in average nocturnal as well as diurnal meal size. It thus appears that even in the face of a sudden increase in energy expenditure resulting from cold exposure, adult rats do not immediately adjust their daily food intake. On the other hand, the adaptive hyperphagic response occurring after cold acclimation is abolished when the energy demand is eliminated, i.e., when the animals are removed from the cold.

Acclimatization

Long-and short-term regulation of feeding patterns in the rat.

Analysis of feeding patterns in rats showed that the amount of food eaten in relatively long intervals (24-72 hr) was correlated with mean meal size and was essentially uncorrelated with meal frequency. Similarly, the regulatory adjustment in daily food intake occurring in response to changes in environmental temperature was shown to be the result of an adjustment in mean meal size, with no change in meal frequency. On the other hand, the amount of food eaten in relatively short intervals (3-12 hr) was shown to be more highly correlated with meal frequency than with mean meal size, and a reliable correlation between meal size and the postmeal interval was obtained. It was also shown that the meal size/postmeal interval regression equation predicts the long-term relation between mean meal size and the amount of food eaten. Take together, these results indicate that meal frequency is controlled largely by short-term regulatory signals and that at least some long-term regulatory signals affect meal size directly.

Animals

Influence of a liquid diet and meal pattern on body weight and body fat in rats.

Rats weighing 110 to 150 g or 250 g initially were utilized in five experiments to determine the effect of the form of the diet (dry versus liquid) and the pattern of feeding (meal-feeding, force-feeding, nibbling, or ad libitum) on body weight gain and on body fat. A high-carbohydrate, 20% casein or 20% lactalbumin diet was fed for 4 to 8 weeks. Consumption of a diet mixed with an equal weight of water increased weight gain in one of three experiments. Body fat content of the rats was not influenced by addition of water to the diet. Neither force-feeding nor meal-feeding influenced body fat gain provided the respective control rats were pair-fed during the initial adaptation period. Likewise, when rats were pair force-fed to ad libitum fed rats without an initial adaptation meal frequency did not influence body fat gain. When meal-fed rats were switched to ad libitum intake their food intake increased to equal that of rats which had been continuously fed ad libitum; however, the rats which had been switched gained more body fat than did rats continuously fed ad libitum. These results suggest that meal frequency may have a minimal influence on body fat accumulation, but that a shift to a higher level of food intake may cause an increased food efficiency and greater rate of fat deposition than in rats continuously fed the higher level of intake.

Adipose Tissue

Patterns of eating as a function of the cost of the meal.

Rats were required to complete fixed ratio schedules (FR 20-FR 2560) of wheel turns to obtain access to food. By decreasing meal frequency and increasing meal size directly as functions of the fixed ratio requirement, animals controlled total daily food intake and body weight relatively constant until the highest ratio requirement was introduced. These functional changes in feeding patterns provide experimental support for theoretical models of optimal feeding strategies. At the highest ratio requirement, as animals lost weight, they increased running and therefore opportunities to feed, however, food intake continued to decrease with increasing exposure to this schedule. As rats on this schedule initiated feeding each time food became available, but did not eat large enough to this schedule. As rats on this schedule initiated feeding each time food became available, but did not eat large enough meals to maintain body weight, it is suggested that activity may interest with satiety mechanisms to produce termination of meals.

Animals

The temporal pattern of feeding over the oestrous cycle of the mouse.

The detailed temporal pattern of feeding in female mice was measured by an automated method over the oestrous cycle whilst feeding on either of two foods differing in stimulus characteristics, but of similar calorific value. The total time spent feeding varied systematically over the cycle, being increased for sweet food and decreased for laboratory chow at the time of sexual receptivity. and increased for both foods towards the end of the cycle. The temporal pattern is analysed into a number of variables, which are seen to alter in different ways over the oestrous cycle. The pro-oestrus disturbance is due to alterations in meal size brought about solely by changes in mean bout length, themselves products of variations in the initial bouts of the meal. Inter-meal interval is unrelated to changes in meal size at this time, allowing the latter to affect food intake. The changes towards the end of the cycle are produced by alterations of meal frequency at constant meal size. It is argued that separable 'phasic' and 'tonic' effects of reproductive condition on feeding may therefore be identified, and that they might possibly have different functions.

Animal Feed

Mechanisms for enhanced feeding in the cold in rats.

The effect of environmental cold upon feeding, food-motivated behavior, and gastric clearance of food was studied in rats. Rats ate liquid diet in either a 5 degrees C or 22 degrees C ambient temperature (TA) following (a) 24-hr food deprivation at TA of either 5 or 22 degrees C, or (b) 0- or 48-hr food deprivation at TA 22 degrees C. Rats ate more at 5 degrees C than at 22 degrees C regardless of the ambient temperature during deprivation. Rats increased feeding in the cold by increasing meal frequency but not meal size. Cold (5 degrees C) TA also enhanced the urge to eat. Rats bar pressed for food more often in the cold TA on a variable interval 30-sec schedule when gastric clearance of food was prevented by a pyloric noose and when food cleared from the stomach normally. Also, quinine adulteration of food suppressed food intake only in the 22 degrees C TA. Cold (5 degrees C) TA enhanced gastric clearance of liquid food within 20 min of ingestion. These results support the view that the peripheral sensation of cold is an adequate stimulus for feeding and that cold TA can stimulate feeding directly by increasing the urge to eat and indirectly, secondary to increased gastric clearance.

Animals

Changing meal patterns and suppression of feed intake with increasing amounts of dietary nonprotein nitrogen in ruminants.

Goats were injected intraruminally during spontaneous meals with ammonium chloride, urea, ammonium lactate, or sodium lactate arranged in a Latin square experimental design randomized for order of treatments. Urea and ammonium injections shortened meal length by 20 to 30%. Rate of eating and meal frequency were reduced. Sodium lactate injections reduced meal size. In cows, meal length and meal size also were measured. Grain concentrate, corn silage, and chopped hay were fed as complete mixed rations. In the concentrates 58+ of the nitrogen was either from soybean meal or urea. Length of the first meal after feeding was reduced from 24.3 min with soybean meal to 12.4 with urea. Meal size was reduced from 3.2 kg to 1.8 kg when urea was fed. Total feed intake was similar, 12.0 kg/day (soybean meal) and 11.6 kg/day (urea) since spontaneous meal number and size were 17 and .30 kg for soybean meal but increased to 23 and .36 kg for urea. The physiological basis for the limit on meal length with urea rations is unknown but is an important factor in successful feeding of urea when eating time is limited for cows.

Ammonium Chloride

Food and water intake, meal patterns and activity of obese and lean Zucker rats following chronic and acute treatment with delta9-tetrahydrocannabinol.

A series of experiments investigated the effects of delta9-THC on food and water intakes and wheel-running activity of Zucker rats. Following chronic drug treatment (15 days), food and water intakes of all rats were suppressed, but intakes and body weights of the obese rats recovered more slowly than those of lean rats. Acute effects of the drug (24 hr) were examined using techniques of meal pattern analysis and were discussed in relation to known patterns of anorectic drug action. The drug-induced anorexia was both delayed and of short duration, with no rebound eating observed for either solid or liquid diets. Both feeding rate and meal size were reduced, but meal frequency was transiently increased. The time of onset of the first meal remained unchanged. The time course of the suppression of feeding was paralleled by a suppression in running-wheel activity. These findings suggest that the drug-induced reduction in food and water intake may be the result of a decreased level of arousal.

Animals

Some factors related to obesity in the Japanese sumo wrestler.

Sumo is an ancient sport in Japan and there are at present over 800 professional sumo wrestlers (rikishis). After entrance into the wrestler society a wrestler takes strenuous daily training together with a very high calorie diet (more than 5,000 cal). Frequency of food intake is twice a day. The average diet of Japanese people contains of 2,279 calories and the meal frequency is generally three times a day. In 96 wrestlers average actual body weight and modified Broca index was 100.4 kg and 143.5%, respectively. In this group the prevalence of overweight with obesity, overweight without obesity, nonoverweight with obesity, and nonoverweight without obesity was 53.4, 39.1, 1.0, and 6.5%, respectively. Also mean serum levels of triglyceride, phospholipid, uric acid, and total protein were significantly higher than those obtained in 89 age-matched healthy males. The incidence of diabetes mellitus, gout, and hypertension in wrestlers was 5.2, 6.3, and 8.3%, respectively, all values being considerably higher than in controls. Weight correlated significantly with skinfold thickness, diastolic blood pressure, total cholesterol, and uric acid in each group. Multiple regression analyses were made treating weight or uric acid as dependent variables in both groups. Obesity, hyperlipidemia, and hyperuricemia in wrestlers were presumed to be caused chiefly by the high calorie diet and partially by the infrequent meal intake.

Adolescent