Association between environmental exposure and CD4+CD25+ regulatory T cells

Background: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. Aim: To compare CD4+/CD25+ T-regulatory cells and forkhead transcription factor Foxp3 expression in asthmatic children allergic to house dust mites (HDM) living in rural and farm areas. Materials and Methods: This was a prospective analysis of 35 children living in farm areas (n = 19) and rural areas (n = 16), aged 8-16, with allergic rhinitis (allergic to dust mites) and newly diagnosed asthma. Surface molecule CD4+CD25+Foxp3+ expression on cultured PBMCs was estimated by flow cytometry using fluorophore-conjugated monoclonal antibodies in each patient. Results: Thirty-five children were included into the analysis: 19 children living in farm areas and 16 in rural areas. Within and between-groups (farm area vs. rural area) differences in CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression did not reach the level of significance. Conclusion: The current analysis showed that CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression was not associated with place of living in asthmatic children sensitive to HDM

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Association between environmental exposure and CD4+CD25+ regulatory T cells.

BACKGROUND: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. AIM: To compare CD4+/CD25+ T-regulatory cells and forkhead transcription factor Foxp3 expression in asthmatic children allergic to house dust mites (HDM) living in rural and farm areas. MATERIALS AND METHODS: This was a prospective analysis of 35 children living in farm areas (n=19) and rural areas (n=16), aged 8-16, with allergic rhinitis (allergic to dust mites) and newly diagnosed asthma. Surface molecule CD4+CD25+Foxp3+ expression on cultured PBMCs was estimated by flow cytometry using fluorophore-conjugated monoclonal antibodies in each patient. RESULTS: Thirty-five children were included into the analysis: 19 children living in farm areas and 16 in rural areas. Within and between-groups (farm area vs. rural area) differences in CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression did not reach the level of significance. CONCLUSION: The current analysis showed that CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression was not associated with place of living in asthmatic children sensitive to HDM.

Effects of a cereal rich in soluble fiber on body composition and dietary compliance during consumption of a hypocaloric diet.

OBJECTIVES: To investigate the effects of oats, a cereal rich in soluble fiber, on body composition changes and dietary compliance during consumption of a weight loss diet. METHODS: Subjects were 41 healthy men and women aged 18 to 78 years. Weight maintenance energy requirements were established over two weeks during consumption of a control diet with low soluble fiber content. Subjects then consumed a hypocaloric diet for six weeks, either consuming a low soluble fiber control diet or a diet containing 45 g/1000 kcal rolled oats, a whole grain cereal rich in soluble fiber (mean energy deficit -895+/-18 kcal/day relative to weight maintenance energy requirements). Changes in body fat and fat-free mass were determined by underwater weighing, and dietary compliance was assessed using the urinary osmolar excretion rate technique. In a final phase of the study, subjects ate ad libitum for six months, and changes in body weight and composition were monitored. RESULTS: There was no significant effect of the oat-containing diet on body weight or composition changes during the hypocaloric regimen or in the subsequent ad libitum period. In addition, fecal energy excretion was not significantly different between groups. However, there were non-significant trends indicating reduced hunger in the oat group compared to controls (frequency of hunger 2.5+/-0.5 vs. 3.6+/-0.4, P=0.1). In addition, fewer oat subjects were non-compliant (four versus seven subjects dropped out or had urinary osmolar excretions greater than 130% of values predicted from dietary intake), but again the difference was not significant. CONCLUSIONS: These results suggest that use of a cereal rich in soluble fiber in a closely monitored hypocaloric feeding regimen does not improve weight loss or dietary compliance. Further studies are needed to examine the possibility that cereals containing soluble fiber may have effects on hunger and dietary compliance that could be important in less tightly controlled protocols than the one described here.

Meal palatability, substrate oxidation and blood glucose in young and older men.

We investigated the effects of food palatability on the thermic effect of feeding (TEF), substrate oxidation and circulating glucose and insulin. Healthy young men (23.4+/-1.0, SD, years, n=10) and older men (69.4+/-1.3, years, n=9) were resident in a metabolic unit for two 2-day study periods. On the second day of each period, they consumed in random order either a palatable test meal containing 2.93 MJ or a nonpalatable control meal containing the same foods in identical amounts but blended and freeze-dried into biscuit form. TEF and respiratory quotient (RQ) were measured over 6 h and blood samples were taken for measurement of glucose and insulin. Age group had no effect on TEF, RQ or circulating glucose other than to delay the time of peak TEF (P<0.002 for both meals). There was no significant effect of meal type on TEF, but RQ and circulating glucose were higher following consumption of the palatable meal (P<0.001 for both parameters). These results suggest that over 6 h postprandial, consumption of palatable foods does not increase TEF, but is instead associated with increased glycemic response and increased carbohydrate oxidation. These changes, combined with previous work on the glycemic index, predict an accelerated return of hunger and increased energy intake at subsequent meals following consumption of palatable vs. control foods. Further studies are needed to examine the possible mechanism for this previously suggested "second meal" effect of diet palatability on energy intake.

Dietary determinants of energy intake and weight regulation in healthy adults.

Until recently, the percentage of energy from dietary fat has been considered a primary determinant of body fatness. This review covers recent studies from our laboratory that challenge this notion. High and low fat diets matched for energy density, palatability and fiber resulted in similar mean voluntary energy intakes over 9 d; analysis of the individual foods in these diets showed that energy density and palatability were significant determinants of energy intake, independent of fat content. Path analysis further revealed that the influence of energy density on energy intake was in part direct, and in part indirect and mediated by palatability. In another study, dietary variety within food groups was shown to be an important predictor of body fatness, and the direction of the association depended on which food groups provided the variety, i.e., the variety of sweets, snacks, condiments, entrees and carbohydrates consumed was positively associated with body fatness, whereas the variety of vegetables was negatively associated. Last, a study of restaurant food and body fatness showed that the frequency of consumption of restaurant food was positively associated with body fatness, independent of education level, smoking status, alcohol intake and physical activity. Restaurant meals tend to be high in fat and low in fiber, and thus energy dense. Restaurants also typically serve a variety of palatable foods in large portions. The increasing variety of high energy foods available and the increasing proportion of household income spent on foods consumed away from home may help explain the U.S. national rising prevalence of obesity.

Overeating in America: association between restaurant food consumption and body fatness in healthy adult men and women ages 19 to 80.

PURPOSE: To examine the association between the frequency of consuming restaurant food and body fatness in adults. RESEARCH METHODS AND PROCEDURES: Usual free-living dietary intake and the frequency of consuming food from seven different restaurant types (fried chicken, burger, pizza, Chinese, Mexican, fried fish, and "other") were assessed by food frequency questionnaire in 73 healthy men and women [ages 19 to 80, body mass index (BMI) 18 to 33]. In addition, body fatness (percent weight) was determined by hydrostatic weighing, and physical activity and other lifestyle parameters were assessed by questionnaire. The relationship between the frequency of consuming restaurant food and body fatness was determined after controlling for age, sex, and other confounders by using multiple regression techniques. RESULTS: Restaurant food consumption averaged 7.5+/-8.5 (Standard Deviation) times/month. After controlling for age and sex, the frequency of consuming restaurant food was positively associated with body fatness (partial r = 0.36, p = 0.003). The strength of this association did not change after controlling for education level, smoking status, and alcohol intake, but after additionally controlling for physical activity, the partial r increased to 0.42 (p = 0.004). Total daily intakes of energy, fat, and fiber were significantly associated with restaurant food consumption frequency (r = 0.59, 0.28, and -0.45, respectively, p = 0.02 to 0.0001). DISCUSSION: The frequency of consuming restaurant food was positively associated with increased body fatness in adults. The increasing proportion of household food income spent on food prepared away from home in the United States may therefore help explain the rising national prevalence of obesity.

Dietary variety within food groups: association with energy intake and body fatness in men and women.

BACKGROUND: Short-term experimental studies suggest that dietary variety may influence body fatness but no long-term human studies have been reported. OBJECTIVE: The purpose of this study was to determine whether dietary variety within food groups influences energy intake and body fatness. DESIGN: Seventy-one healthy men and women (aged 20-80 y), who provided accurate reports of dietary intake and completed a body-composition assessment, were studied. RESULTS: Dietary variety was positively associated with energy intake within each of 10 food groups (r = 0.27-0.56, P < 0.05). In multiple regression analysis with age and sex controlled for, dietary variety of sweets, snacks, condiments, entrées, and carbohydrates (as a group) was positively associated with body fatness (partial r = 0.38, P = 0.001) whereas variety from vegetables was negatively associated (partial r = -0.31, P = 0.01) (R2 = 0.46, P < 0.0001). In separate models, both a variety ratio (variety of vegetables/variety of sweets, snacks, condiments, entrées, and carbohydrates) and percentage dietary fat were significant predictors of body fatness (controlled for age and sex, partial r = -0.39 and 0.31, respectively, P < 0.01). However, dietary fat was no longer significantly associated with body fatness when the variety ratio and dietary fat were included in the same model. CONCLUSIONS: Our data, coupled with those of previous short-term studies, suggest that a high variety of sweets, snacks, condiments, entrées, and carbohydrates coupled with a low variety of vegetables promotes long-term increases in energy intake and body fatness. These findings may help explain the rising prevalence of obesity.

Relationship between circulating leptin and energy expenditure in adult men and women aged 18 years to 81 years.

Recent studies suggest that leptin may be an important metabolic signal for energy regulation in rodents, but the role of leptin in human energy regulation remains uncertain. Because adaptive variations in energy expenditure play an important role in human energy regulation, we investigated the relationship between leptin and energy expenditure parameters in 61 weight-stable men and women aged 18 years to 81 years who were not obese. Measurements were made of circulating leptin in the fasting state, body fat and fat free mass, resting metabolic rate (n = 61), free-living total energy expenditure (n = 52), and the thermic effect of feeding (n = 33). After statistically accounting for age, body fat, and fat free mass, there was no association between leptin and any measured energy expenditure parameter. In addition, there was no effect of age on the relationship between circulating leptin and body fat mass. These results indicate that physiological variations in circulating leptin are not linked with adaptive variations in energy expenditure in humans, in contrast to indications of this phenomenon in the ob/ob mouse.

Effects of age on energy expenditure and substrate oxidation during experimental overfeeding in healthy men.

Relatively little is known about the influence of age on energy regulation during energy imbalance. We compared the effects of overfeeding on changes in energy expenditure, substrate oxidation, and energy deposition between young men (age 23.7 +/- 1.1 [SEM] years) and older men (age 70.0 +/- 7.0) of normal body weight who were leading unrestricted lives. Changes in total energy expenditure, resting energy expenditure (REE), the thermic effect of feeding (TEF), respiratory quotient (RQ), and body energy content were determined in response to overeating by 4.09 +/- 0.07 Megajoule (MJ)/day for 21 days in 16 healthy subjects consuming a typical diet. After excluding data from one young subject with unusual results and adjusting for individual differences in excess energy intake, there was a tendency towards a smaller increase in REE in older men compared to the young men (p = .07) which was accounted for by their lower fat-free mass (p = .016). There was also a significantly smaller increase in resting energy expenditure averaged over fasting and fed states (i.e, REE + TEF) with overfeeding in older men than in young men (p < .01). Combined, these smaller increases in energy expenditure with overfeeding in the older subjects averaged an estimated 365 kilojoule (kJ)/day (8.9% of the excess energy intake) (p < .02). There were also significant effects of age on fasting RQ (p < .001) and the change in RQ with overfeeding (p < .001), but no significant increase in energy expenditure for physical activity and thermoregulation with overfeeding in either age-group. These results are consistent with the suggestion that older individuals experience both a reduction in the ability to increase energy expenditure, and an alteration in the pattern of substrate utilization, in response to overfeeding. These changes may promote cumulative increases in body energy during normal cycles of positive energy balance unless compensated for by adaptive variations in energy intake.

Effects of age on energy expenditure and substrate oxidation during experimental underfeeding in healthy men.

Relatively little is known about the influence of age on energy regulation during energy imbalance. We compared the effects of underfeeding on changes in energy expenditure, substrate oxidation, and body energy loss between young men (age 22.0 +/- 0.9 [SEM] years) and older men (age 66.0 +/- 1.8) who were leading unrestricted lives. Changes in total energy expenditure (TEE), resting energy expenditure (REE), the thermic effect of feeding (TEF), respiratory quotient, and body energy loss were determined in response to undereating by 3.17 +/- 0.16 Megajoule (MJ)/day for 21 days in 19 healthy subjects consuming a typical diet. No significant effects of age were observed in changes in TEE, REE, TEF, or body energy loss in response to underfeeding. Thus, older men do not appear to have any impairment of energy conservation during negative energy balance compared to young men. This normal pattern of energy conservation during undereating together with the previously demonstrated reduction in energy dissipation during overeating can be predicted to promote body fat deposition in older men during the cycles of positive and negative energy balance that occur during normal life. This finding may help to explain the increased body fat mass in older individuals.

Influence of age on energy requirements.

The effects of aging on energy requirements and energy expenditure were investigated in 35 healthy young men (mean +/- SE age, 22.7 +/- 0.6 y) and elderly men (68.0 +/- 1.5 y). Over a 10-d metabolic balance study, measurements were made of metabolizable energy intake for weight maintenance, total energy expenditure, resting energy expenditure, and thermic effect of feeding. Values for both metabolizable energy intake and total energy expenditure were significantly higher than the current recommended dietary allowance for energy in both age groups (P < 0.01). Total energy expenditures were 14.48 +/- 0.65 and 11.26 +/- 5.40 MJ/d in young and elderly men, respectively. The difference in total energy expenditure between the groups was accounted for by a significant decrease in all the major components of expenditure. These results suggest that the current recommended dietary allowances for energy may underestimate the usual energy needs of healthy adult men.

Dietary energy requirements of young and older women determined by using the doubly labeled water method.

There is little information on the effects of age on energy requirements in women. This issue was investigated in a cross-sectional study of 10 normal-weight young women aged 25.2 +/- 1.1 y (mean +/- SEM) and 10 normal-weight older women aged 74.0 +/- 1.4 y. In a 9-d study, measurements were made of free-living total energy expenditure (TEE) by using the doubly labeled water technique, body composition by using hydrodensitometry, and resting energy expenditure (REE) by using indirect calorimetry. Mean values for reported levels of strenuous activity were within the expected range in both groups (31 +/- 13 min/d in the young group and 7 +/- 2 min/d in the older group). Energy requirements expressed as the ratio of TEE to REE were 1.80 +/- 0.10 and 1.62 +/- 0.06 (P < 0.01) in the young and older group, respectively. When values for REE predicted from body weight (pREE) were used, as suggested in the current recommended dietary allowances (RDAs), the ratios of TEE to pREE in the two groups were 1.85 +/- 0.10 and 1.54 +/- 0.04 (P < 0.05). The RDAs significantly under-predicted the energy requirements of the young group (P < 0.05), but there was no significant underprediction in the older group. Although obtained in a relatively small number of subjects, these results provide no evidence to indicate that the current RDAs underestimate the energy requirements of older women, in contrast with previous observations of an underestimation of energy requirements by the RDAs in older men.

Control of food intake in older men.

OBJECTIVE: To investigate the effects of aging on mechanisms of body energy regulation and thereby determine the causes of unexplained weight loss in older persons, a factor predisposing to premature death and disability. DESIGN: Dietary intervention study. SETTING: Metabolic ward and outpatient. PARTICIPANTS: The subjects were 35 healthy younger and older men of normal body weight consuming a diet of typical composition and performing usual activities. MAIN OUTCOME MEASURES: Subjects were either overfed by a mean (+/- SD) of 4.09 (+/- 0.26) MJ/d (n = 17) or underfed by 3.17 (+/- 0.68) MJ/d (n = 18) for 21 days. Measurements were made of changes in body weight, body composition, and energy expenditure during overfeeding or underfeeding, and of subsequent voluntary nutrient intakes and changes in body weight. RESULTS: There was no significant effect of aging on changes in body composition, body weight, or energy expenditure with overfeeding or underfeeding. However, following overfeeding, younger men exhibited spontaneous hypophagia, whereas the older men did not (mean [+/- SD] changes in energy intake relative to control values were -2.11 [+/- 2.18] and 1.55 [+/- 2.11] MJ/d, respectively; P = .006). As a result, the younger men lost the excess body weight gained during overfeeding but the older men did not. Similarly, following underfeeding, the younger men exhibited hyperphagia while the older men did not (mean [+/- SD] changes in energy intake relative to control values were 1.88 [+/- 2.31] and -0.52 [+/- 1.54] MJ/d, respectively; P = .02), and as a result the older men failed to regain the weight lost during underfeeding. CONCLUSIONS: These results in 35 men suggest that aging may be associated with a significant impairment in the ability to control food intake following overeating or undereating. Since overeating and undereating occur routinely as part of the normal pattern of energy regulation, the findings reported herein may help to explain the vulnerability of older persons to unexplained weight gain and weight loss.

Energy expenditure, aging and body composition.

We investigated the importance of adaptive variations in energy expenditure in the regulation of energy balance in young and elderly men of normal body weight leading unrestricted lives. Changes were measured in total and resting energy expenditure and body composition in response to overeating by approximately 4.2 MJ/d or undereating by 3.3 MJ/d for 21 d in 39 young and elderly men consuming a typical diet. In the young men, an average of 85-90% of the excess energy intake during overeating was deposited. During underfeeding, mobilization of body energy compensated for an average of 65% of the energy deficit in these subjects. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (+0.63 +/- 0.20 MJ/d, P < 0.01) and decreased during underfeeding (-0.42 +/- 0.12 MJ/d), but at least some of these changes were due to the obligatory expenditure associated with nutrient assimilation. There was no significant change in energy expenditure for physical activity or thermoregulation from overfeeding or underfeeding. Preliminary results indicate that aging had no effect on responses to overfeeding or underfeeding. These findings suggest that adaptive variations in energy expenditure are not the major determinant of energy regulation in young adults of normal body weight and that, instead, energy balance is maintained on a day-to-day basis through the control of nutrient intakes.

What are the dietary energy needs of elderly adults?

The energy requirements of healthy elderly men were investigated by measuring total energy expenditure (TEE), body composition and resting energy expenditure (REE), using 2H2(18)O techniques and indirect calorimetry during ten days when a weight maintaining diet was consumed. Values for TEE/REE (1.75 +/- 0.05, s.e.) were significantly higher than the recommended dietary allowances (RDAs) for energy in this age group, as were previously reported values for TEE/REE in a group of young men in the same experimental protocol. There was a significant negative association between TEE/REE (a physical activity indicator) and body fat mass. Combining data from the elderly men in this study and the young men studied previously, age and TEE/REE together accounted for 73% of the variation in body fat mass between individuals. These results lend additional weight to the suggestion that the current RDAs for energy may significantly under-estimate usual energy requirements. They also indicate that the low levels of energy expenditure suggested by the RDAs may favour unnecessarily high levels of body fat mass and that increased levels of energy expenditure are desirable.

Underfeeding and body weight regulation in normal-weight young men.

The mechanisms of energy regulation invoked by moderate dietary restriction were investigated in seven healthy young men of normal body weight leading unrestricted lives. Following a baseline period of weight maintenance, subjects were underfed by 806 +/- 162 (mean +/- SE) kcal/day for 21 days. Changes in total energy expenditure (TEE) and resting energy expenditure (REE) and subsequent voluntary nutrient intakes were measured. The REE, averaged for fasting and fed states, decreased during underfeeding by 100 +/- 29 kcal/day (P less than 0.01). TEE decreased nonsignificantly by 296 +/- 170 kcal/day, equivalent to an average of 37% of the decrease in energy intake. Body energy stores were estimated to decrease by 510 +/- 172 kcal/day (P less than 0.03), thus compensating for 63% of the dietary energy deficit on average. Voluntary energy intake following dietary restriction increased above the initial amount required for body weight maintenance, was proportional to the weight loss during underfeeding (P less than 0.03), and was associated with a rapid regain of weight lost during underfeeding. These results indicate that energy balance is regulated by adaptive variations in both energy intake and energy expenditure in normal-weight young men leading unrestricted lives but do not support the hypothesis that energy-wasting mechanisms contribute substantially to body energy regulation.

Dietary energy requirements of young adult men, determined by using the doubly labeled water method.

We examined the hypothesis that current recommendations on dietary energy requirements may underestimate the total energy needs of young adult men, by measuring total energy expenditure (TEE) and resting energy expenditure (REE) in 14 weight-maintaining healthy subjects leading unrestricted lives. TEE and body composition were measured by using 2H(2)18O, and REE was measured by using indirect calorimetry. All subjects had sedentary full-time occupations and participated in strenuous leisure activities for 34 +/- 6 (SE) min/d. TEE and REE were 14.61 +/- 0.76 and 7.39 +/- 0.26 MJ/d, respectively, and 202 +/- 2 and 122 +/- 2 kJ.kg-1.d-1. There were significant relationships between TEE and both body fat-free mass (r = 0.732, P less than 0.005) and measured REE (r = 0.568, P less than 0.05). Measured TEE:REE values were significantly higher than the recommended energy requirement (1.98 +/- 0.09, compared with 1.55 or 1.67, P less than 0.005). These results are consistent with the suggestion that the current recommended energy intake for young adult men may underestimate total energy needs.

Energy expenditure and subsequent nutrient intakes in overfed young men.

We investigated the mechanisms of body weight regulation in young men of normal body weight leading unrestricted lives. Changes in total and resting energy expenditure, body composition, and subsequent voluntary nutrient intakes in response to overeating by 4,230 +/- 115 (SE) kJ/day (1,011 +/- 27 kcal/day) for 21 days were measured in seven subjects consuming a typical diet. On average, 85-90% of the excess energy intake was deposited (with 87% of this amount in fat and 13% in protein on average). There was no detectable difference between individuals in susceptibility to energy deposition. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (mean +/- SE, 628 +/- 197 kJ/day, P less than 0.01), but at least some of this amount was obligatory expenditure associated with nutrient assimilation. No significant increase in energy expenditure for physical activity or thermoregulation resulted from overfeeding. Thus energy expenditure did not substantially adapt to increased energy intake. However, significant decreases in voluntary energy intake (1,991 +/- 824 kJ/day, P less than 0.05) and fat intake (48 +/- 11 g/day, P less than 0.01) followed overeating, indicating that adaptive changes in nutrient intakes can contribute significantly to body weight regulation after overeating.