Overconsumption Of Calories Research Articles

The Auto‐Digestive Hypothesis: A New Mechanism For Development of Leptin Resistance And Obesity

Obesity is a major health problem and leads to increased morbidity and mortality from cardiovascular complications. Leptin acts on the brain to regulate food intake through its interactions with its receptor (ObR). Defects in leptin production and in ObR leads to the development of obesity, however, obesity is associated with high circulating leptin levels concomitantly with leptin resistance. The mechanism leading to leptin resistance is unknown. We hypothesize that calorie over consumption can lead to increased proteolytic activity in the brain promoting cleavage of key receptors governing food intake. Wister rats were fed high fat diet (HF) for 10 weeks. A control group was provided with regular chow (NC). At 10 weeks, rats were sacrificed and the brain was removed for determination of proteolytic activity and levels of the extracellular domain of the ObR. HF rats had significantly higher body weight compared to NC. Zymography showed increased proteolytic activity in HF rat's brain, which was accompanied with reduced levels of the extracellular domain of the ObR. Our results also suggest MMP‐9 as a possible mediator of ObR cleavage. We conclude that calorie over‐consumption can promote proteolytic activity and cleavage of key receptors in the brain; therefore can mediate the development of obesity. The origin of the proteolytic activity in HF rat's brain remains to be elucidated.

Animal models of NASH: Getting both pathology and metabolic context right

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of referral to liver clinics, and its progressive form, non-alcoholic steatohepatitis (NASH), can lead to cirrhosis and end-stage liver disease. The main risk factors for NAFLD/NASH are the metabolic abnormalities commonly observed in metabolic syndrome: insulin resistance, visceral obesity, dyslipidemia and altered adipokine profile. At present, the causes of progression from NAFLD to NASH remain poorly defined, and research in this area has been limited by the availability of suitable animal models of this disease. In the past, the main models used to investigate the pathogenesis of steatohepatitis have either failed to reproduce the full spectrum of liver pathology that characterizes human NASH, or the liver pathology has developed in a metabolic context that is not representative of the human condition. In the last few years, a number of models have been described in which the full spectrum of liver pathology develops in an appropriate metabolic context. In general, the underlying cause of metabolic defects in these models is chronic caloric overconsumption, also known as overnutrition. Overnutrition has been achieved in a number of different ways, including forced feeding, administration of high-fat diets, the use of genetically hyperphagic animals, or a combination of these approaches. The purpose of the present review is to critique the liver pathology and metabolic abnormalities present in currently available animal models of NASH, with particular focus on models described in approximately the last 5 years.

Food Safety for the 21st Century

THROUGHOUT HISTORY, HUMAN HEALTH HAS DEpended on food supply. Recognition that food can pose a major threat to human health is also centuries old. Federal regulation to reduce food contamination in the United States began in the early 20th century, with the adoption of the Pure Food and Drug Act and the Meat Inspection Act of 1906 that regulated food purity and required content disclosure. Since then, additional regulatory measures and industrial improvements have further reduced contamination, although food-borne pathogens still cause the deaths of 5000 individuals a year in the United States. But the most rapidly growing food-related threat to health today is not microbes, but overconsumption of calories, sugar, salt, and unhealthy fat. In the United States, nearly a third of adults are obese, a proportion that has doubled in 20 years. Unhealthy diet and physical inactivity are second only to tobacco as underlying causes of death. Overweight and obesity currently account for more than 1 in 6 cancer deaths in the United States. Globally, the 10 leading underlying causes of disabilityadjusted life-years lost include high blood pressure (which is in large part diet-related), overweight, high cholesterol, and low intake of fruits and vegetables. Echoing the public outcry about food sanitation a century ago, there is increasing public distrust of food and the food industry, evidenced by books and films such as Fast Food Nation and Supersize Me. However, governments have been slow to use effective public policy to protect citizens from diet-related chronic diseases. Instead, efforts to promote healthy eating have generally been limited to guidelines and education, which are relatively weak interventions. To have a substantial effect on diet-related health problems, as did public health measures in response to microbial threats, stronger actions are needed.

Stress and Sex Influences on Food‐seeking Behaviors

Stress increases the drive to consume calorically dense preferred foods suggesting an exogenous factor that may induce caloric overconsumption and weight gain. As females show heightened stress sensitivity and present with increased rates of obesity, we hypothesized that stress-induced increases in the motivation for preferred foods may be a sex-specific predisposing factor for weight gain. To investigate this hypothesis, we have developed a buried food paradigm that permits the measurement of sex differences and effects of chronic variable stress (CVS) on the latency to uncover and the consumption of a preferred food pellet without the requisite caloric restriction required in traditional operant conditioning tasks. In our studies, females consistently showed latencies that were twice as fast as males to locate the buried pellet in limited access tests. Interestingly, during stress exposure, male latencies decreased to that of control female levels. Male and female mice showed a significant effect of stress, three- and fourfold, respectively, on increased consumption of the preferred food during testing. These results support a basal sex difference in behaviors toward a preferred food, and a possible role of stress sensitivity in the drive and intake of such foods. Sex differences in the role stress plays in these behaviors may provide insight into underlying mechanisms related to an increased obesity risk.

Effects of sucrose, glucose and fructose on peripheral and central appetite signals

In the Western world, consumption of soft drinks has increased the last three decades and is partly responsible for the epidemic-like increase in obesity. Soft drinks, originally sweetened by sucrose, are now sweetened by other caloric sweeteners, such as fructose. In this study, we investigated the short-term effect of sucrose, glucose or fructose solutions on food intake and body weight in rats, and on peripheral and central appetite signals. Rats received water containing either of the sugars and standard rat chow for two weeks. Rats receiving water alone and standard chow were controls. All rats offered the sugar solutions increased their total caloric intake. The increased caloric intake occurred despite the fact that the rats offered either of the sugar solutions consumed less chow. As a consequence of the increased caloric intake, the sugar-drinking rats had elevated serum levels of free fatty acids, triglycerides and cholesterol. In addition, consuming sugar solutions resulted in increased serum leptin, decreased serum PYY and down-regulated hypothalamic NPY mRNA. Serum ghrelin was increased in rats receiving fructose solution. Moreover, consumption of sucrose or fructose solution resulted in up-regulated hypothalamic CB1 mRNA. Hypothalamic POMC mRNA was down-regulated in rats receiving glucose or fructose. In conclusion, consumption of glucose, sucrose or fructose solution results in caloric overconsumption and body weight gain through activation of hunger signals and depression of satiety signals as well as activation of reward components. The weight-promoting effect of these sugar solutions may possibly be ameliorated by the down-regulation of NPY mRNA and increased serum leptin.

Partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice

Partial leptin deficiency is not uncommon in the general population. We hypothesized that leptin insufficiency could favor obesity, nonalcoholic steatohepatitis (NASH), and other metabolic abnormalities, particularly under high calorie intake. Thus, mice partially deficient in leptin (ob/+) and their wild-type (+/+) littermates were fed for 4 mo with a standard-calorie (SC) or a high-calorie (HC) diet. Some ob/+ mice fed the HC diet were also treated weekly with leptin. Our results showed that, when fed the SC diet, ob/+ mice did not present significant metabolic abnormalities except for elevated levels of plasma adiponectin. Under high-fat feeding, increased body fat mass, hepatic steatosis, higher plasma total cholesterol, and glucose intolerance were observed in +/+ mice, and these abnormalities were further enhanced in ob/+ mice. Furthermore, some metabolic disturbances, such as blunted plasma levels of leptin and adiponectin, reduced UCP1 expression in brown adipose tissue, increased plasma liver enzymes, beta-hydroxybutyrate and triglycerides, and slight insulin resistance, were observed only in ob/+ mice fed the HC diet. Whereas de novo fatty acid synthesis in liver was decreased in +/+ mice fed the HC diet, it was disinhibited in ob/+ mice along with the restoration of the expression of several lipogenic genes. Enhanced expression of several genes involved in fatty acid oxidation was also observed only in ob/+ animals. Leptin supplementation alleviated most of the metabolic abnormalities observed in ob/+ fed the HC diet. Hence, leptin insufficiency could increase the risk of obesity, NASH, glucose intolerance, and hyperlipidemia in a context of calorie overconsumption.

Nonalcoholic fatty liver disease and mitochondrial dysfunction

Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

Enhancement of intragastric acid stability of a fat emulsion meal delays gastric emptying and increases cholecystokinin release and gallbladder contraction

Preprocessed fatty foods often contain calories added as a fat emulsion stabilized by emulsifiers. Emulsion stability in the acidic gastric environment can readily be manipulated by altering emulsifier chemistry. We tested the hypothesis that it would be possible to control gastric emptying, CCK release, and satiety by varying intragastric fat emulsion stability. Nine healthy volunteers received a test meal on two occasions, comprising a 500-ml 15% oil emulsion with 2.5% of one of two emulsifiers that produced emulsions that were either stable (meal A) or unstable (meal B) in the acid gastric environment. Gastric emptying and gallbladder volume changes were assessed by MRI. CCK plasma levels were measured and satiety scores were recorded. Meal B layered rapidly owing to fat emulsion breakdown. The gastric half-emptying time of the aqueous phase was faster for meal B (72 +/- 13 min) than for meal A (171 +/- 35 min, P < 0.008). Meal A released more CCK than meal B (integrated areas, respectively 1,095 +/- 244 and 531 +/- 111 pmol.min.l(-1), P < 0.02), induced a greater gallbladder contraction (P < 0.02), and decreased postprandial appetite (P < 0.05), although no significant differences were observed in fullness and hunger. We conclude that acid-stable emulsions delayed gastric emptying and increased postprandial CCK levels and gallbladder contraction, whereas acid-instability led to rapid layering of fat in the gastric lumen with accelerated gastric emptying, lower CCK levels, and reduced gallbladder contraction. Manipulation of the acid stability of fat emulsion added to preprocessed foods could maximize satiety signaling and, in turn, help to reduce overconsumption of calories.

Effect of flavour of liquid Ensure diet supplement on energy intake in male SD rats

Outbred male Sprague–Dawley rats were provided with one of the four flavours of the liquid diet, Ensure, in addition to chow pellets, to examine whether differences in flavour lead to differences in energy intake i.e. degree of over-consumption. For half the rats, the Ensure supplement was provided for 14 days and then withdrawn for the final 8 days of the study, whereas the remaining animals were allowed to consume Ensure for 22 days. All four flavours of Ensure, chocolate, vanilla, coffee and asparagus, induced a sustained increase in daily energy intake of approximately 15%. There was an effect of flavour on initial consumption of the Ensure diet, with coffee and asparagus flavours being consumed less avidly than vanilla or chocolate. However, this effect was short-lived. Overall, there was no effect of flavour on body weight gain, energy intake from Ensure, total energy intake, body composition, or measured blood hormones and metabolites. Withdrawal of Ensure resulted in reductions in body weight gain, total energy intake, fat but not lean tissue mass, and concentrations of blood leptin, non-esterified fatty acids and triglycerides, but there was no effect of the flavour of Ensure previously supplied on any of these parameters. The ability of the liquid diet, Ensure, to stimulate long-term caloric over-consumption is not due to its flavouring. Rather, other attributes of Ensure must be more important, such as its intrinsic flavour, liquid formulation, macronutrient composition, and ease of ingestion, digestion and absorption.

Childhood obesity, prevalence and prevention

Childhood obesity has reached epidemic levels in developed countries. Twenty five percent of children in the US are overweight and 11% are obese. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. The mechanism of obesity development is not fully understood and it is believed to be a disorder with multiple causes. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. In general, overweight and obesity are assumed to be the results of an increase in caloric and fat intake. On the other hand, there are supporting evidence that excessive sugar intake by soft drink, increased portion size, and steady decline in physical activity have been playing major roles in the rising rates of obesity all around the world. Consequently, both over-consumption of calories and reduced physical activity are involved in childhood obesity.Almost all researchers agree that prevention could be the key strategy for controlling the current epidemic of obesity. Prevention may include primary prevention of overweight or obesity, secondary prevention or prevention of weight regains following weight loss, and avoidance of more weight increase in obese persons unable to lose weight. Until now, most approaches have focused on changing the behaviour of individuals in diet and exercise. It seems, however, that these strategies have had little impact on the growing increase of the obesity epidemic. While about 50% of the adults are overweight and obese in many countries, it is difficult to reduce excessive weight once it becomes established. Children should therefore be considered the priority population for intervention strategies. Prevention may be achieved through a variety of interventions targeting built environment, physical activity, and diet. Some of these potential strategies for intervention in children can be implemented by targeting preschool institutions, schools or after-school care services as natural setting for influencing the diet and physical activity. All in all, there is an urgent need to initiate prevention and treatment of obesity in children.

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.

Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity

Obesity is a major epidemic, but its causes are still unclear. In this article, we investigate the relation between the intake of high-fructose corn syrup (HFCS) and the development of obesity. We analyzed food consumption patterns by using US Department of Agriculture food consumption tables from 1967 to 2000. The consumption of HFCS increased > 1000% between 1970 and 1990, far exceeding the changes in intake of any other food or food group. HFCS now represents > 40% of caloric sweeteners added to foods and beverages and is the sole caloric sweetener in soft drinks in the United States. Our most conservative estimate of the consumption of HFCS indicates a daily average of 132 kcal for all Americans aged > or = 2 y, and the top 20% of consumers of caloric sweeteners ingest 316 kcal from HFCS/d. The increased use of HFCS in the United States mirrors the rapid increase in obesity. The digestion, absorption, and metabolism of fructose differ from those of glucose. Hepatic metabolism of fructose favors de novo lipogenesis. In addition, unlike glucose, fructose does not stimulate insulin secretion or enhance leptin production. Because insulin and leptin act as key afferent signals in the regulation of food intake and body weight, this suggests that dietary fructose may contribute to increased energy intake and weight gain. Furthermore, calorically sweetened beverages may enhance caloric overconsumption. Thus, the increase in consumption of HFCS has a temporal relation to the epidemic of obesity, and the overconsumption of HFCS in calorically sweetened beverages may play a role in the epidemic of obesity.

Palatability-induced hyperphagia increases hypothalamic Dynorphin peptide and mRNA levels

Opioid involvement in regulating the intake of highly palatable diets was studied by examining the effect of feeding either a cornstarch-based diet (CHO) or a high fat diet containing sucrose (Fat/Sucrose) on hypothalamic opioid levels. Rats received either CHO ad libitum, Fat/Sucrose ad libitum, Fat/Sucrose pair-fed to the caloric intake of CHO, or Fat/Sucrose at 60% of ad libitum Fat/Sucrose intake. Animals receiving Fat/Sucrose ad libitum consumed more calories and gained more weight than animals receiving CHO ( P < 0.001). Relative to CHO, ad libitum intake of Fat/Sucrose elevated proDynorphin mRNA levels in the arcuate and Dynorphin A 1–17 levels in the paraventricular nucleus (PVN) ( P < 0.05), but did not affect arcuate mRNA levels of proEnkephalin or proOpiomelanocortin (POMC), or PVN levels of Met-Enkephalin or β-Endorphin. Pair-feeding the Fat/Sucrose diet to the level of intake of the CHO diet resulted in levels of proDynorphin and Dynorphin A 1–17 that were similar in the two diet groups. Pair-feeding Fat/Sucrose reduced mRNA levels of proDynorpin, proEnkephalin and POMC, and Dynorphin A 1–17 levels, relative to ad libitum feeding of Fat/Sucrose. Met-Enkephalin and β-Endorphin were not affected by dietary treatment. Feeding Fat/Sucrose at 60% of ad libitum intake resulted in mRNA levels of proDynorphin, proEnkephalin and POMC, and Dynorphin A 1–17 levels that were similar to those observed in CHO group. Hypothalamic Dynorphin A 1–17 and proDynorphin mRNA levels are stimulated by feeding a highly palatable diet rich in fat and sucrose. The increased synthesis may be due in part to a palatability-induced overconsumption of calories. Caloric restriction of the same diet decreases mRNA levels of proDynorphin, proEnkephalin and POMC, as well as levels of Dynorphin A 1–17.

Hyperplastic Response of Adipose Tissue to Caloric Overconsumption in Sexually Mature Chickens

Two experiments were conducted to determine the hyperplastic response of adipose tissue from sexually mature chickens in response to caloric overconsumption. In the first experiment, birds were either force-fed or allowed to consume feed ad libitum, whereas in the second experiment, a feed-restriction regimen was also implemented. In both experiments feeding treatments were applied for 19 consecutive days, and a diet high in energy and low in protein was fed to all birds to promote lipogenesis. To monitor adipocyte dynamics, birds in Experiment 1 received an intramuscular injection of [methyl-3 H]thymidine on Day 15, whereas in Experiment 2 birds were injected on Days 1 and 10.In both Experiments 1 and 2, body weight gain and percentage weight gain were greater in the force-fed birds. Furthermore, the retroperitoneal (abdominal), and right sartorial fat depots increased in weight as a result of force-feeding, and there were concomitant increases in total adipocyte DNA content and total radiotracer uptake by these tissues. The results indicate that expansion of adipose tissue in sexually mature chickens is not restricted solely to cellular hypertrophy, but periodic hyperplastic activity also occurs in response to caloric overconsumption.

Obesity: Thermodynamic principles in perspective

The energy balance equation applicable to all living organisms was used as a framework on which to construct a critical review of some of the more controversial aspects of the obesity problem. The equation matches energy intake against all the known forms of work that the body does in utilizing that energy, including external and internal work and the work of adipose tissue synthesis (stored energy). Equations representing everyday living conditions, resting, fasting and basal conditions were constructed. The equation applicable to everyday living (working, non-fasting) was used to develop a set of model paradigms to illustrate some of the devices that can be invoked to decrease expenditure and conserve energy. These served as models of how obesity can arise in the absence of calorie overconsumption. The same equation was then used to create a set of opposite paradigms showing how obesity can be prevented by increasing expenditure to waste energy and stabilize body weight when challenged by hyperphagia. In order to see caloric intake and the various work terms in their proper quantitative relationships it was necessary to assign numerical values to the equation. These were selected from published reports of caloric values representative of a non-obese adult of average size engaged in a typical white collar occupation. It was then easy to adjust these assigned values commensurate with the objectives described in the preceding paragraph. Since obesity research is hampered by a confusing array of metabolic interactions it was essential to alter only one of the energy terms at a time, excluding all metabolic interactions except for those unavoidable ones dictated by the laws of thermodynamics. Only in this way could we see the body's multiple energy forms in clear perspective with regard to their real quantitative significance in the energy balance sheet and their potential impact on body weight. Creating these models gave us the added advantage of enabling us better to evaluate the scientific literature because the data we generated, although theoretical, served as excellent standards against which to compare the real data that have emanated from research laboratories. Our general conclusions are: • Calorie overconsumption must be regarded as the major contributor to body weight gain, and reduced consumption as the first and most effective line of defense. The simple algebraic relationship which balances this simple source of the body's energy supply against a multiplicity of energy expenditure forms makes the conclusion inevitable. • Physical exercise has a far smaller impact on weight reduction in obese people than is generally believed. • The reasons are defined mainly in terms of the thermodynamic relationship between exercise and other obligatory channels of energy expenditure. • A major obstacle to experimentally verifying the hypothesis that obesity can arise as the result of an increased metabolic efficiency is the basal metabolic rate. • Measurement difficulties are most likely the basis for the current controversy surrounding diet-induced thermogenesis and luxuskonsumption. • Some major pitfalls in experimental methodology are identified. • Some caveats for future investigations are described.

Hyperphagia: A Necessary Precondition to Obesity?

Weight-gain is generally attributed to a caloric imbalance resulting from hyperphagia. However, this attribution is often made without observing caloric intakes during the initial accumulation of fat stores. Instead, this conclusion is drawn because many obese organisms overeat, and overconsumption is sufficient to cause weight-gain. The literature is reviewed, specifically those studies on the onset of caloric overconsumption relative to weight-gain and the accumulation of fat during food restriction, which suggests that hyperphagia is not necessary for animals prone to obesity to become fatter and heavier. It is observed that animals with genetically- and surgically-induced obesity often become fat prior to hyperphagia and continue to gain even if food restricted to subnormal levels. Overconsumption does speed this gain.

Area postrema lesions cause overconsumption of palatable foods but not calories

Rats with lesions of the area postrema and immediately adjacent solitary nucleus consume greater amounts of highly palatable food during short exposures than do control rats. When a highly palatable substance (cookies or glucose solutions) is available continuously along with laboratory chow, lesioned rats exhibit average 24 hour calorie intakes which are not different from those of control rats. Nevertheless, the lesioned animals ingest a significantly greater proportion of total calories as the highly palatable substances than do control rats. The data suggest that lesions involving the area postrema and adjacent nucleus of the solitary tract enhance intake of highly palatable food without causing overconsumption of calories.

Effects of nutrient cues on formula intake in 5-week-old infants

This study was designed to test: (1) whether an increase in lipid density during the course of formula feeding would depress the infants' volume and caloric intake; and (2) whether the infants would exhibit differential adjustments in intake between high caloric lipid formula and isocaloric carbohydrate formula. Ten five-month-old infants were given a control (Enfamil 20) formula and two other experimental formulas with comparatively elevated concentrations in either lipids or carbohydrates. The infants were tested on five consecutives days using counter-balanced treatments combining two formulas each day. Changing lipid density in the course of a feeding did not prevent the infants from overconsumption of calories; but the high caloric lipid formula did suppress intakes of the heavier babies.