High-intensity sweeteners and energy balance

Recent epidemiological evidence points to a link between a variety of negative health outcomes (e.g. metabolic syndrome, diabetes and cardiovascular disease) and the consumption of both calorically sweetened beverages and beverages sweetened with high-intensity, non-caloric sweeteners. Research on the possibility that non-nutritive sweeteners promote food intake, body weight gain, and metabolic disorders has been hindered by the lack of a physiologically-relevant model that describes the mechanistic basis for these outcomes. We have suggested that based on Pavlovian conditioning principles, consumption of non-nutritive sweeteners could result in sweet tastes no longer serving as consistent predictors of nutritive postingestive consequences. This dissociation between the sweet taste cues and the caloric consequences could lead to a decrease in the ability of sweet tastes to evoke physiological responses that serve to regulate energy balance. Using a rodent model, we have found that intake of foods or fluids containing non-nutritive sweeteners was accompanied by increased food intake, body weight gain, accumulation of body fat, and weaker caloric compensation, compared to consumption of foods and fluids containing glucose. Our research also provided evidence consistent with the hypothesis that these effects of consuming saccharin may be associated with a decrement in the ability of sweet taste to evoke thermic responses, and perhaps other physiological, cephalic phase, reflexes that are thought to help maintain energy balance.     

Dietary self-selection of golden hamsters in response to acute food deprivation and chronic food restriction

Adult male golden hamsters were maintained on either Purine Rat Chow (Chow diet) or a self-selection diet consisting of high-protein chow, pure fat, and pure carbohydrate (Choice diet). In Experiment 1, animals were deprived of food for single periods of up to 48 hr. Animals on the Chow diet did not increase intake at any time after deprivation; animals on the Choice diet selectively increased their consumption of fat-derived calories and increased their total caloric intake during the first 6 hr of refeeding, but not thereafter. The nature of the diet did not influence the rate at which animals regained weight following deprivation. In Experiment 2, hamsters were placed on food-restriction schedules (access to food either for 1 hr/day only or on alternate days only) until they lost 20% of starting body weight. Chow-fed animals demonstrated little or no change in food intake either during or after food restriction. Hamsters on the Choice diet consumed more calories and lost weight more slowly than did chow-fed animals during 1-hr/day feeding; intake of fat-derived calories was elevated during restriction. Choice hamsters increased total caloric intake only towards the end of the alternate-days restriction schedule. Choice hamsters were hyperphagic following both types of food-restriction schedules, but no increased preference for fat-derived calories was observed. Factors influencing food consumption of hamsters in response to deprivation and restriction are discussed.     

Hypermetabolism in a triple-transgenic mouse model of Alzheimer's disease

A common feature of Alzheimer's disease (AD) is weight loss, even though there is often an increase in food intake in AD patients. The reasons for this weight loss are unknown, but may be due to increased energy expenditure (metabolic rate) or a reduction in energy intake. This was investigated in the present study, using a triple-transgenic (3xTgAD) mouse model of AD. Two-month-old 3xTgAD mice displayed greater food intake (17%) and body weight (34%) but no difference in metabolic rate, as compared with nontransgenic controls (non-Tg). At 12 months of age, 3xTgAD mice still consumed more food (30%), but their body weight was significantly lower (15%) than non-Tg controls. This reduction in body weight was accompanied by a significant rise in metabolic rate, indicated by greater oxygen consumption (24%) and carbon dioxide production (29%); the effects were also observed in 18-month-old 3xTgAD mice. These data demonstrate for the first time the existence of a hypermetabolic state in an experimental model of AD, but whether this can explain the weight loss observed in AD patients remains to be determined.     

Behavioral and physiologic responses to caloric restriction in mice

The purpose of the review is to highlight the influences of ambient temperature (T(a)) and caloric restriction (CR) on metabolism, cardiovascular function and behavior in mice. Standard vivarium ambient temperatures (T(a)?23 degrees C) are a mild cold stress for mice requiring elevated metabolic rate and food intake. Increasing T(a) into the zone of thermoneutrality (TMN?29-33 degrees C) markedly reduces food intake, metabolic rate, heart rate (HR) and blood pressure in mice. Mice are members of a diverse, yet unique group of homeothermic animals that respond to thermal and energetic challenges by allowing body temperature (T(b)) to fall to less than 31 degrees C, a condition known as torpor. In mice housed at standard T(a), torpor is induced by a single night of fasting or a few days of CR. The mechanisms responsible for initiating torpor are related to reduced caloric availability, but do not require leptin. Mice housed at TMN and subjected to CR exhibit physiologic reductions in metabolic rate and HR, but do not appear to enter torpor. Finally, mice exhibit differential locomotor activity responses during CR that depends on T(a). At standard T(a), mice display increased light-phase home-cage activity with CR. This response is virtually eliminated when CR is performed at TMN. We suggest that researchers using mice to investigate energy homeostasis and cardiovascular physiology carefully consider the influence of T(a) on physiology and behavior.     

Age-related changes in adaptive macronutrient intake in swimming male and female Lou rats

To evaluate the age-related changes in capacity to adjust the nutrient intake to needs, self-selecting male and female Lou/C/jall rats of 4, 6, 12, 16 and 23 months of age were submitted to a swimming exercise. They were given 6 consecutive days of moderate intensity training (3 x 15 minutes per day). Exercise and postexercise periods were compared with results from the pretraining period. During swimming, a body weight loss and a decrease in both caloric intake and fat selection were observed. This effect was more marked in older groups compared to 4 month-old groups. An increase in protein intake was observed in females, specially in older groups, whereas no effect was seen in males. The ability to increase caloric ingestion and regain weight during the postexercise period decreased with advancing age and was better in females than in males. We also showed an age-related effect on the recovery of initial nutrient intake rate that was more pronounced and more precocious for males. Moreover, males tended to decrease their protein intake, whereas females significantly increased it. The present findings suggest a decrease of capacity of adjusting feeding behavior to metabolic needs in aged rats, may be due to a deterioration of the central control of food intake.     

A moderate swimming exercise regularly performed throughout the life induces age and sex-related modifications in adaptive macronutrients choice

The ability of laboratory rats to adapt food intake to needs is well-known. The present study investigates changes in this adaptive behavior when animals grow old. A cohort of male and female Lou/c/jall rats was regularly submitted to an exercise throughout their life (6 consecutive days of moderate intensity training (3×15 min/day)). Caloric intake and macronutrients selection during exercise and post-exercise periods were compared to the pre-training period. During swimming, a decrease in both caloric intake and fat selection was observed and an increase in protein intake was specifically seen in female groups. However, males were unable to modify the diet composition (macronutrient rate) from 16 months of age, whereas females were able to do it until 24 months of age. The present results suggest a sex-dependant loss of capacity of adjusting feeding behavior to metabolic needs when animals grow old, may be due to a deterioration of the central control of food intake.     

Changes in energy balance following smoking cessation and resumption of smoking in women

Caloric intake, resting metabolic rate (RMR), leisure-time physical activity, and sensitivity and preference for sweet taste were prospectively examined in 7 female smokers across 3 weeks during periods of normal smoking (Week 1), complete cessation (Week 2), and resumption of smoking (Week 3). Energy balance changed significantly across weeks, as caloric intake increased (largely as a result of alcohol consumption) and RMR decreased during cessation, followed by decreased caloric intake and increased RMR with resumption of smoking. Activity and taste sensitivity and preference remained unchanged. Smoking cessation may thus cause rapid change in energy balance, which is quickly reversed on resumption of smoking.     

A role for sweet taste: calorie predictive relations in energy regulation by rats

Animals may use sweet taste to predict the caloric contents of food. Eating sweet noncaloric substances may degrade this predictive relationship, leading to positive energy balance through increased food intake and/or diminished energy expenditure. These experiments were designed to test the hypothesis that experiences that reduce the validity of sweet taste as a predictor of the caloric or nutritive consequences of eating may contribute to deficits in the regulation of energy by reducing the ability of sweet-tasting foods that contain calories to evoke physiological responses that underlie tight regulation. Adult male Sprague-Dawley rats were given differential experience with a sweet taste that either predicted increased caloric content (glucose) or did not predict increased calories (saccharin). We found that reducing the correlation between sweet taste and the caloric content of foods using artificial sweeteners in rats resulted in increased caloric intake, increased body weight, and increased adiposity, as well as diminished caloric compensation and blunted thermic responses to sweet-tasting diets. These results suggest that consumption of products containing artificial sweeteners may lead to increased body weight and obesity by interfering with fundamental homeostatic, physiological processes.     

Effects of fasting and refeeding on the metabolic response to a standard meal in man

Summary Measurements of resting and exercising metabolic rate were made on eight subjects (five male, three female) before and after consumption of a standard liquid meal (1.67 MJ).This test was conducted after a day of complete fast and again after a day of overeating (average intake, 19.8 MJ). There were no significant changes in resting or exercising metabolic rate due to the previous day's energy intake. The resting thermic effect (post-prandial rise in metabolic rate) of the standard meal was similar on both test days but the exercising thermic effect was 50% greater after the day of overeating. It was concluded that the metabolic response to food in exercising subjects may be affected by the previous day's energy intake but the overall energetic efficiency of the body at rest and during exercise is unaffected.     

Memory inhibition and energy regulation

At a simple behavioral level, food intake and body weight regulation depend on one's ability to balance the tendency to seek out and consume food with the ability to suppress or inhibit those responses. Accordingly, any factor that augments the tendency to engage in food seeking and eating or that interferes with the suppression of these behaviors could produce (a) caloric intake in excess of caloric need; (b) increases in body weight leading to obesity. This paper starts with the idea that excess body weight and obesity stem from a failure or degradation of mechanisms that normally function to inhibit eating behavior. Unlike previous approaches, we focus not on failures of traditional physiological (e.g., neural, hormonal) regulatory control mechanisms, but on disruptions of inhibitory learning and memory processes that may help to regulate energy intake. This view of energy dysregulation as a type of "learning disorder" leads us to the hippocampus, a brain structure that has long been regarded as an important substrate for learning and memory and which we think may be critically involved with a specific type of memory inhibition function that could contribute to the suppression of food intake. With this focus, the search for environmental origins of the current obesity epidemic in Western populations is directed toward factors that alter hippocampal functioning. We conclude by offering a preliminary account of how consumption of foods high in saturated fats might lead to impaired hippocampal function, reduced ability to inhibit caloric intake and, ultimately, to increased body weight.     

Changes in food intake in response to alterations in the ambient temperature: Modifications by previous thermal and nutritional experience

1. The influence of ambient temperature on ad libitum food intake has been investigated in piglets weaned at 2 weeks and kept in the hot (35 degrees C) or the cold (10 degrees C) on a high or low energy intake for 6 weeks. Further, the extent to which food intake was correlated with fasting body temperatures and resting metabolic rate was also examined. 2. The amount of food eaten in a single meal was recorded daily in two series of tests. In Test I, measurements were made both at the normal living temperature and after 2 and 24 h at thermal neutrality (25 degrees C). In Test II, the animals were examined at 25 degrees C over a 4 day period. Resting metabolic rate and body temperatures were also measured, immediately before the measurement of food intake. 3. Food intake was much greater at 10 than at 35 degrees C, but even at thermal neutrality it was significantly higher for those which had been in the cold. This was true for periods of between 2h and 4 days at 25 degrees C. Although food intake was not correlated with skin or core temperatures, there was an indication of a correlation with metabolic rate, particularly at thermal neutrality. 4. The results show that long-term cold exposure has a lasting effect on food intake, even at thermal neutrality, and it is suggested that this may be related to hormonal changes.     

The effects of repeated cycles of weight loss and regain in rats

This study examined the metabolic effects of weight cycling, i.e., repeated periods of weight loss followed by regain. There were three groups of adult, male Sprague-Dawley rats: (1) Chow Controls (a normal weight control group fed chow throughout); (2) Obese Controls (animals fed a high-fat diet throughout); and (3) Obese Cycling (obese animals cycled through two bouts of caloric restriction and refeeding). The cycled animals showed significant increases in food efficiency (weight gain/kcal food intake) in the second restriction and refeeding periods compared to the first, i.e., weight loss occurred at half the rate and regain at three times the rate in the second cycle. Several physiological changes were associated with this cycling effect. At the end of the experiment, cycled animals had a four-fold increase in food efficiency compared to obese animals of the same weight who had not cycled. These data suggest that frequent dieting may make subsequent weight loss more difficult. The possible metabolic and health consequences of "yo-yo" dieting are discussed.     

Role of caloric homeostasis and reward in alcohol intake in Syrian golden hamsters

The Syrian golden hamster drinks alcohol readily, but only achieves moderate blood alcohol levels, and does not go through withdrawal from alcohol. Because the hamster is a model of caloric homeostasis, both caloric content and reward value may contribute to the hamster's alcohol consumption. The current study examines alcohol consumption in the hamster when a caloric or non-caloric sweet solution is concurrently available and caloric intake in the hamster before, during, and after exposure to either: alcohol, sucrose or saccharin. In Experiments 1 and 2, hamsters were given access to alcohol (15% v/v) and water; once alcohol consumption steadied, a bottle containing an ascending concentration of sucrose (99-614 mM) or saccharin (2-10 mM), or water was added. In Experiment 3, hamsters were given access to alcohol (15% v/v), sucrose (614 mM), saccharin (4 mM), or a second water bottle for 14 days. After the second bottle was removed, measurements continued for 14 days. Sucrose exposure suppressed alcohol consumption at concentrations lower in calories than the alcohol solution. Saccharin exposure failed to suppress alcohol consumption. Exposure to sucrose and alcohol but not saccharin decreased food intake. Decreased alcohol consumption in response to a caloric sweetener and decreased food intake during alcohol exposure support that alcohol consumption by the hamster is mediated by caloric content. However, suppression of alcohol intake by a sucrose solution of lower caloric content and the equivalent intake of individual alcohol, sucrose and saccharin solutions support a role for reward value in alcohol consumption.     

Feeding patterns of endurance athletes

Summary Feeding pattern was studied in 13 long distance runners, eight cyclists and eight sedentary men. The timing of the food and fluid intakes, the kind and the amount of food and fluids taken, the body weight (BW), and the exercise schedules were recorded on 3 or 4 successive days under ad libitum conditions of feeding and drinking. The subjects remained in energy and water balance, since the BW measured in the morning during the observation periods did not change significantly. The total caloric intake was 13 876 kJ per day in the runners and 26 282 kJ per day in the cyclists, exceeding the estimated basic metabolic rate by 103% and 250% respectively. The total water intakes were 33 and 36 ml·kg^–1·24 h^–1. The athletes consistently showed a nibbling pattern, characterized by frequent eating and drinking (average 8–10 per day). In the runners 63% of eating and drinking were synchronized, in the cyclists only 49% (p<0.01). In both groups drinking occurred most frequently in the morning, at noontime and in the evening. After 8 p.m. 45% of the total daily fluid intake occurred. In all likelihood the fluid intake followed an underlying circadian rhythm. The total intake frequency was determined by the total caloric needs.Supported by the Bundesinstitut für Sportwissenschaften, Köln     

Effects of exercise-training on the thermic effect of food and body fatness of adult women

Resting metabolic rate (RMR), thermic effect of food (TEF), aerobic capacity (VO2max), body fat, and food intake were measured in 10 healthy women before and after a 10 week graded exercise program of jogging. Pretraining TEF was a linear function of VO2max. Following exercise training, the women showed a significant increase (20%) in VO2max and loss (10.4%) of body fat; body weight did not change. Fat loss was directly related to changes in VO2max and RMR. The women showed a wide variation of changes in RMR (-21 to +2%) and TEF (-32 to +66%) from their pretraining levels. The changes in RMR and TEF were significantly positively correlated with improvements in VO2max. Analyses using multiple regression techniques, indicated that the changes in RMR and TEF accounted for 96.2% of the total variation in the changes of VO2max. Analyses of food intake indicated that diet composition (but not caloric intake) was highly related to the changes in VO2max, RMR, TEF and body fatness. Present results support further our hypothesis, that VO2max is an important physiological index of dietary thermogenesis and fat loss of individuals of normal body weight and fatness. Possible nutritional and physiological factors that may explain the wide variation in RMR and TEF of the women are discussed.     

Consumption of a high-fat diet induces central insulin resistance independent of adiposity

Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad libitum food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin's inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF- but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA.     

Effects of estrous cycles and ovarian steroids on body weight and energy expenditure in Syrian hamsters

In Experiment 1, highly significant changes were observed over the estrous cycle in body weight gain, but not in food intake, daytime resting oxygen consumption or brown fat thermogenesis in Syrian hamsters. In Experiments 2 and 3, body weight and composition, food intake, resting oxygen consumption, and brown fat thermogenesis were measured following estradiol or estradiol plus progesterone treatment in ovariectomized hamsters. The significant changes in body weight could not be explained by changes in food intake, and were not accompanied by significant alterations in daytime oxygen consumption or brown fat thermogenic activity. In Experiment 4, resting oxygen consumption and body weight were measured every 6 hours over the estrous cycle. There was a striking absence of the usual nocturnal peak in resting oxygen consumption on the night of estrus (the night of the largest body weight gain). However, brown fat thermogenic activity did not differ among groups of hamsters killed on different nights of the estrous cycle. Estradiol-induced changes in energy storage may be mediated by changes in the daily rhythm of energy expenditure which are not dependent on alterations in brown fat thermogenesis.     

Ovariectomy Interferes with Proteomes of Brown Adipose Tissue in Rats

Postmenopausal women exhibit a higher prevalence of obesity due to decreased energy expenditure and increased food intake compared to their premenopausal counterparts. Brown adipose tissue (BAT) plays a key role in energy homeostasis, thus providing us with appealing therapeutic targets in obesity. However, how BAT proteomes are altered in response to low levels of estrogen remains unclear. To better understand the underlying mechanisms between the postmenopausal state and BAT proteomic changes, our study aimed to investigate the effect of ovariectomy on the BAT proteome. In this study, eight-week-old female Sprague Dawley rats were randomly allocated into bilateral ovariectomy (Ovx) and sham operation (Sham) groups. Mass spectrometry was used for proteomics assay and Ingenuity Pathway Analysis was applied to examine the differentially regulated proteins. Of the 1,412 identified proteins, 18 proteins were significantly upregulated, whereas 36 proteins were significantly downregulated in the Ovx group as compared to the Sham group. Our findings demonstrate that the proteins involved in BAT morphology, the browning of white adipose tissue, and metabolic substrates for thermogenesis were regulated by ovariectomy. The dysregulation of proteins by ovariectomy might be related to the disruption of BAT function in the postmenopausal status. Understanding how BAT proteomes are altered in response to ovariectomy may illuminate novel therapeutic strategies for the management of postmenopausal weight gain in the future.     

Inverse relationship between brown fat thermogenesis and meal size: The thermostatic control of food intake revisited

This study examines a new hypothesis whereby heat production from brown fat in response to eating may serve as a feedback signal for satiety. To test this hypothesis, in vitro respiration rate of brown adipose tissue (BAT) was determined in relation to the voluntary caloric intake of the preceding test meal. This relationship was examined as a function of meal composition and of obesity. It was found that in rats fed a high fat diet, as well as in two types of obese rats (VMH and Zucker), respiration rate per 100 mg tissue was significantly reduced, and energy intake of the preceding test meal increased compared to rats receiving a low fat diet or to respective lean rats. These data lend support to a brown fat mediated thermostatic hypothesis for the control of food intake.