Sex-based differences in the behavioral and neuronal responses to food

Sex-based differences in food intake related behaviors have been observed previously. The objective of this study was to examine sex-based differences in the behavioral and neuronal responses to food. 22 women and 21 men were studied. After 6 days of controlled eucaloric feeding, ad libitum energy intake (EI) was measured for 3 days. Appetite ratings using visual analog scales were obtained before and after each meal. Functional magnetic resonance imaging was performed in the overnight fasted state on the last day of eucaloric feeding while subjects were presented visual stimuli of food and neutral non-food objects. While hunger and prospective consumption were not different between sexes, women had higher post-meal satiety ratings and dietary restraint than men. Images of hedonic foods resulted in significantly greater activation of lateral and dorsolateral prefrontal cortex (DLPFC) and parietal cortex in women as compared to men. No brain regions were more activated in men as compared to women. Men increased their EI during the ad libitum diet phase. While measures of appetite or feeding behaviors did not correlate with either neuronal activation or subsequent EI, DLPFC activation in response to hedonic foods was negatively correlated with EI. In summary, greater prefrontal neuronal responses to food cues in women may suggest increased cognitive processing related to executive function, such as planning, guidance or evaluation of behavior. Finally, increased DLPFC activation, perhaps relating to inhibitory cognitive control in response to food cues may be a better predictor of food intake than behavioral measures.     

Anabolic neuropeptides

The hypothalamus and other brain regions that control energy homeostasis contain neuronal populations that produce specific neuropeptides which have experimental effects on feeding behavior and body weight. Here, we describe examples of neuropeptides that exert 'anabolic' effects, notably stimulation of feeding and increased body weight. Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) are inhibited by leptin and insulin, and thus are stimulated in states of energy deficit and fat loss, e.g., underfeeding. NPY neuronal overactivity contributes to enhanced hunger and food-seeking activity under these conditions. The lateral hypothalamic area (LHA) contains specific neuronal populations that affect feeding in different ways. Neurons expressing the appetite-stimulating peptide orexin A are stimulated by starvation (but not food restriction) and by hypoglycemia, but only if food is withheld. Orexin neurons are apparently activated by low glucose but are promptly inhibited by visceral feeding signals, probably mediated via vagal sensory pathway and the nucleus of the solitary tract (NTS); a short-term role in initiating feeding seems most likely. Other LHA neurons express melanin-concentrating hormone (MCH), which transiently increases food intake when injected centrally. MCH neurons may be regulated by leptin, insulin and glucose. Glucose-sensing neurons in the hypothalamus and elsewhere are sensitive to other cues of nutritional state, including visceral satiety signals (transmitted via the vagus) and orexin A. Thus, long- and short-term humoral and neural signals interact with each other to meet diverse nutritional needs, and anabolic neuropeptides are important in the overall integration of energy homeostasis. Clarifying the underlying mechanisms will be essential to understanding normal energy balance and the pathogenesis and treatment of disorders, such as obesity and cachexia.     

Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity

Intake of saturated fats and simple carbohydrates, two of the primary components of a modern Western diet, is linked with the development of obesity and Alzheimer's Disease. The present paper summarizes research showing that Western diet intake is associated with cognitive impairment, with a specific emphasis on learning and memory functions that are dependent on the integrity of the hippocampus. The paper then considers evidence that saturated fat and simple carbohydrate intake is correlated with neurobiological changes in the hippocampus that may be related to the ability of these dietary components to impair cognitive function. Finally, a model is described proposing that Western diet consumption contributes to the development of excessive food intake and obesity, in part, by interfering with a type of hippocampal-dependent memory inhibition that is critical in the ability of animals to refrain from responding to environmental cues associated with food, and ultimately from consuming energy intake in excess of that driven solely by caloric need.     

Oral and postoral determinants of food reward

Tasty high-fat and high-sugar foods induce overeating and obesity in animals. To separate the roles of oral and postoral factors in food preference and consumption, recent studies have used an "electronic esophagus" preparation. With this system, when an animal drinks a flavored solution, it controls the infusion of nutrients directly into its stomach through an implanted catheter. Improving the palatability of the flavored solution increases solution intake, infused nutrient intake, and weight gain. Changing the composition of the infused nutrient (e.g., fat-carbohydrate ratio) can also alter energy intake when flavor cues are held constant. In addition, animals learn to associate flavor cues with the postoral effects of nutrients, which can significantly increase flavor preference and acceptance. In some but not all cases, conditioned preferences are associated with increased hedonic evaluation of the nutrient-paired flavor. Flavor preference conditioning by nutrients can occur in chow-sated animals and is not dependent upon an energy-depleted state. Thus, food reward is determined by oral and postoral stimuli and may override the homeostatic regulation of energy balance.     

The effects of glucocorticoids on feeding behavior in rats

Glucocorticoids have major effects on food intake, however, the underlying mechanisms are poorly understood. This article highlights data on the changes that occur when glucocorticoids are removed by adrenalectomy, and the effects of central and systemic administered glucocorticoids on feeding behavior in rats. Next, animal data on the interaction of glucocorticoids with insulin on intake of comfort foods are addressed and the hypothesis that glucocorticoids modify feeding behavior, whereas insulin modifies the choice of food is discussed. Finally a view is presented that hormonal and vagal signals generated when (comfort) food is consumed will affect the corticotropin-releasing factor (CRF) brain network important for the response to stress and the regulation of feeding. With a society, where stress is experienced daily and comfort food is found at every street corner, it will be vital to understand the interactions between the systems that react to stress and regulate feeding behavior to fight the obesity epidemic.     

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.     

Interactions between the "cognitive" and "metabolic" brain in the control of food intake

If the new environment and modern lifestyle cause obesity in individuals with thrifty genes by increasing energy intake, it is important to know by what mechanisms hyperphagia occurs and why energy balance is not kept in check by the homeostatic regulator. The argument is developed that procuring and ingesting food is an evolutionarily conserved survival mechanism that occupies large parts of the brain's computing capacity including not only the hypothalamus but also a number of cortico-limbic structures. These forebrain systems evolved to engage powerful emotions for guaranteed supply and ingestion of beneficial foods from a sparse and often hostile environment. They are now simply overwhelmed with an abundance of food and food cues that is no longer interrupted by frequent famines. After briefly reviewing structure and functions of the relevant cortico-limbic structures and the better-known hypothalamic homeostatic regulator, the review focuses mainly on interactions between the two systems. Although several cortico-limbic processes are sensitive to metabolic depletion and repletion signals, it appears that they are underlying the same reversible leptin resistance that renders hypothalamic circuits insensible to continuously high leptin levels during periods of feast. It is hypothesized that this naturally occurring leptin resistance allowed temporary neutralization of satiety mechanisms and evolved as a response to survive subsequent periods of famine. With today's continuous and abundant food availability for a segment of the population, the powerful cognitive processes to eat and the resulting overweight can partially escape negative feedback control in prone individuals most strongly expressing such thrifty genes.     

Relationships between human thirst, hunger, drinking, and feeding

There is a widely held view that hunger prompts feeding to ensure energy needs are met, while thirst cues drinking to address hydration requirements. However, recent changes in the nature of the food supply and eating patterns have raised questions about the functionality of these relationships with respect to maintaining energy balance. The increasing consumption of energy-yielding beverages and foods with diluted energy density, through the use of ingredients such as high-intensity sweeteners and fat replacers, poses new challenges to presumed homeostatic energy regulatory mechanisms. This review draws on findings from a recent observational study and other published evidence to explore whether shifts of food composition and use patterns may be disrupting relationships between thirst, hunger, drinking, and eating, resulting in positive energy balance (e.g., drinking low satiety, energy-yielding beverages in response to hunger). The observational study entailed collecting hourly appetitive ratings and dietary recalls from 50 adults for seven consecutive days. These data reveal a clear bimodal daily hunger pattern, whereas thirst is stronger and more stable throughout the day. Further, approximately 75% of fluid intake occurs peri-prandially, with the majority derived from energy-yielding beverages. While there is published evidence that drinking is responsive to feeding, support for the view that drinking is the more tightly regulated behavior is stronger. Our data indicates that, due to a number of plausible factors, neither absolute values nor changes of hunger or thirst are strong predictors of energy intake. However, it is proposed that stable, high thirst facilitates drinking, and with the increased availability and use of energy-yielding beverages that have low satiety properties, can promote positive energy balance. There are marked individual differences in mean daily hunger and thirst ratings with unknown implications for energy balance.     

The shifting beverage landscape

STOREY, M.L. The shifting beverage landscape. PHYSIOL BEHAV, 2010. — Simultaneous lifestyle changes have occurred in the last few decades, creating an imbalance in energy intake and energy expenditure that has led to overweight and obesity. Trends in the food supply show that total daily calories available per capita increased 28% since 1970. Total energy intake among men and women has also increased dramatically since that time.Some have suggested that intake of beverages has had a disproportional impact on obesity. Data collected by the Beverage Marketing Corporation between 1988-2008 demonstrate that, in reality, fewer calories per ounce are being produced by the beverage industry. Moreover, data from the National Cancer Institute show that soft drink intake represents 5.5% of daily calories. Data from NHANES 1999-2003 vs. 2003-06 may demonstrate a shift in beverage consumption for age/gender groups, ages 6 to > 60 years.The beverages provided in schools have significantly changed since 2006 when the beverage industry implemented School Beverage Guidelines. This voluntary action has removed full-calorie soft drinks from participating schools across the country. This shift to lower-calorie and smaller-portion beverages in school has led to a significant decrease in total beverage calories in schools.These data support the concept that to prevent and treat obesity, public health efforts should focus on energy balance and that a narrow focus on sweetened beverages is unlikely to have any meaningful impact on this complex problem.     

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.     

Energy density and portion size: their independent and combined effects on energy intake

The energy density (kcal/g) and the portion size (g) of foods have been identified as two properties of foods that can modulate energy intake. Recent studies have shown that when either the energy density or the portion size of foods is increased, energy intake increases. Within a meal, when both factors are increased simultaneously, their effects are independent and add together to increase energy intake. On the other hand, reducing the energy density of a first course, while increasing the volume that is consumed, leads to a decrease in energy intake at the entire meal. The mechanisms by which both factors exert their influence are not well understood but likely include cognitive and orosensory factors as well as physiological controls related to gastric distention and gastric emptying. Findings from studies in this area of research provide evidence that the energy density and the portion size of foods are important determinants of energy intake. An environment in which the food supply is ample and large portions of energy-dense foods are readily available to consumers can contribute to an overconsumption of calories.     

The effects of exercise on the neuronal response to food cues

Increased physical activity is associated with successful long-term weight loss maintenance due to mechanisms likely more complex than simply increased energy expenditure. The impact of physical activity on the central regulation of food intake may be an important mechanism of this effect. The objective of this study was to examine the effects of exercise training and acute exercise on the neuronal response to food cues as well as eating behaviors. fMRI was performed in the fasted state at baseline and again after a 6 month progressive exercise intervention (supervised, 5 days/wk) both with and without an acute exercise bout in 12 overweight/obese (5 women, 7 men; BMI 33 ± 4 kg/m(2)) healthy adults. fMRI data were acquired while subjects were presented with visual stimuli of foods of high hedonic value as compared to neutral control objects. Questionnaires on eating behaviors, ratings of appeal and desire for foods, and ratings of appetite (hunger, satiety, prospective intake) using visual analog scales were also performed at baseline and again after the 6-month exercise intervention. While only a trend was observed for a reduction in body weight (102 ± 5 to 99 ± 6 kg, p=0.09), a significant reduction in fat mass was observed (36.4 ± 2.8 to 33.7 ± 3.2 kg, p=0.04), although as expected changes in fat mass were variable (-10.0 to +3.7 kg). Chronic exercise was associated with a reduction in the neuronal response to food, primarily in the posterior attention network and insula. A significant positive correlation between the change in fat/body mass and the change in insula response to food cues with chronic exercise was observed. An acute exercise bout attenuated the effects of chronic exercise. The exercise intervention, however, did not impact any of the measures of appetitive behavior. In summary, despite no effects on behavioral measures of appetite, chronic exercise training was associated with attenuation in the response to visual food cues in brain regions known to be important in food intake regulation. The insula, in particular, appears to play an important role in the potential exercise-induced weight loss and weight loss maintenance.     

Leptin resistance and the response to positive energy balance

Animals readily reduce food intake and normalize body weight following a period of involuntary overfeeding, suggesting that regulatory systems are engaged to defend against excess weight gain. However, these data exist in the background of an ongoing obesity epidemic, where the ready availability of palatable, energy dense foods often leads to obesity. Currently we know very little about the mechanisms underlying the normalization of body weight following involuntary overfeeding, nor do we fully understand why select individuals successfully remain lean despite living in an obesigenic environment. Recent progress in the study of leptin signaling indicates that manipulations which enhance leptin sensitivity reduce food intake and attenuate diet-induced obesity, while reductions in leptin signaling predispose to obesity. While it remains unclear whether a failure or insufficiency in the weight regulatory system contributes to obesity, this work highlights the importance of this system for the regulation of body weight and its potential value for the treatment of obesity. Nonetheless, it is necessary to more clearly identify those mechanisms that protect lean individuals from weight gain and mediate the normalization of body weight that follows involuntary overfeeding, because it is only with this knowledge that we can clearly determine whether obesity is dependent on, or independent of, a failure in the weight regulatory system.     

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.     

Control of energy homeostasis by insulin and leptin: Targeting the arcuate nucleus and beyond

As the obesity epidemic, diabetes mellitus type 2, and associated comorbidities show no signs of abating, large efforts have been put into a better understanding of the homeostatic control mechanisms involved in regulation of body weight and energy homeostasis. For decades, the hypothalamic arcuate nucleus (ARC), which integrates peripheral signals and modulates appetite and metabolism, has been the focus of investigation. Besides these basic homeostatic circuits, food palatability and reward are thought to be major factors involved in the regulation of food intake. Highly palatable food is easily available, and is ingested even when there is no metabolic need for it. Thus, overriding of the homeostatic control systems by the cognitive, rewarding, social, and emotional aspects of palatable food may contribute to the obesity epidemic. This review aims to provide an updated view, how insulin and leptin as signals originating from the periphery of the body and communicating energy availability to the CNS act not only on ARC neurons, but also directly control the activity of neuronal circuits in control of food-associated reward mechanisms.     

The effects of exercise on the neuronal response to food cues

Increased physical activity is associated with successful long-term weight loss maintenance due to mechanisms likely more complex than simply increased energy expenditure. The impact of physical activity on the central regulation of food intake may be an important mechanism of this effect. The objective of this study was to examine the effects of exercise training and acute exercise on the neuronal response to food cues as well as eating behaviors. fMRI was performed in the fasted state at baseline and again after a 6 month progressive exercise intervention (supervised, 5 days/wk) both with and without an acute exercise bout in 12 overweight/obese (5 women, 7 men; BMI 33 ± 4 kg/m²) healthy adults. fMRI data were acquired while subjects were presented with visual stimuli of foods of high hedonic value as compared to neutral control objects. Questionnaires on eating behaviors, ratings of appeal and desire for foods, and ratings of appetite (hunger, satiety, prospective intake) using visual analog scales were also performed at baseline and again after the 6-month exercise intervention. While only a trend was observed for a reduction in body weight (102 ± 5 to 99 ± 6 kg, p = 0.09), a significant reduction in fat mass was observed (36.4 ± 2.8 to 33.7 ± 3.2 kg, p = 0.04), although as expected changes in fat mass were variable (− 10.0 to + 3.7 kg). Chronic exercise was associated with a reduction in the neuronal response to food, primarily in the posterior attention network and insula. A significant positive correlation between the change in fat/body mass and the change in insula response to food cues with chronic exercise was observed. An acute exercise bout attenuated the effects of chronic exercise. The exercise intervention, however, did not impact any of the measures of appetitive behavior. In summary, despite no effects on behavioral measures of appetite, chronic exercise training was associated with attenuation in the response to visual food cues in brain regions known to be important in food intake regulation. The insula, in particular, appears to play an important role in the potential exercise-induced weight loss and weight loss maintenance.     

The relationship between dietary energy density and energy intake

Much of the research in ingestive behavior has focused on the macronutrient composition of foods; however, these studies are incomplete, or could be misleading, if they do not consider the energy density (ED) of the diet under investigation. Lowering the ED (kcal/g) by increasing the volume of preloads without changing macronutrient content can enhance satiety and reduce subsequent energy intake at a meal. Ad libitum intake or satiation has also been shown to be influenced by ED when the proportions of macronutrients are constant. Since people tend to eat a consistent weight of food, when the ED of the available foods is reduced, energy intake is reduced. The effects of ED have been seen in adults of different weight status, sex, and behavioral characteristics, as well as in 3- to 5-year-old children. The mechanisms underlying the response to variations in ED are not yet well understood and data from controlled studies lasting more than several days are limited. However, both population-based studies and long-term clinical trials indicate that the effects of dietary ED can be persistent. Several clinical trials have shown that reducing the ED of the diet by the addition of water-rich foods such as fruits and vegetables was associated with substantial weight loss even when patients were not told to restrict calories. Since lowering dietary energy density could provide effective strategies for the prevention and treatment of obesity, there is a need for more studies of mechanisms underlying the effect and ways to apply these findings.     

Variety in the diet enhances intake in a meal and contributes to the development of obesity in the rat

Male and female rats were given three palatable, high energy foods either simultaneously or in succession during three 40 min courses. Both simultaneous and successive variety enhanced energy intake compared to the intake of single palatable foods, which was itself enhanced compared to the intake of chow. Rats deprived of food for 24 hr showed a compensatory increase in chow intake (84%) but only a 20% increase in intake in the single palatable food conditions, and no increase in the variety conditions. Male and female rats showed a similar response to variety and deprivation. The effect of variety on body weight was also examined in rats offered either chow, or chow and one palatable food, or chow and three palatable foods in succession (changed every 12 hr) or simultaneously, for seven weeks. All rats offered the palatable foods were hyperphagic compared to chow-fed controls. Rats given the simultaneous but not the successive variety diet were more hyperphagic than the other palatable food groups and showed significantly greater body weight and fat gains. The availability of a variety of foods is an important factor in the amount eaten in the meal and in the etiology of obesity.