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Obesity:
A Worldwide epidemic
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Index to the article Note:
the numbers between brackets correspond to the reference number included
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here) At the same time, in today's body-conscious society, overweight individuals are subjected to diverse degrees of subjective and objective discrimination. This causes them social adjustment disorders that range from moderate to severe. Motivated by the desire for career advancement and a better self-image, and/or to avoid health problems, overweight individuals flock to any weight control center offering a cure for the disease. In
addition to a lowered self-esteem that can lead to mental instability,
obese individuals also must cope with external and internal threats
(122).
Some
diseases are often associated with obesity. The most important disorders
where obesity appears to play a role in precipitating (or aggravating)
the disease are: Two studies reported that obese young women reported significant dissatisfaction and worry about their weight and the shape of their bodies. Klesges reported similar results among college students. He concluded these results may negatively affect these individuals' quality of life (494). Stunkard
and Mendelson concluded "it makes no difference whether the person
in also talented, wealthy or intelligent; weight is his only matter
of concern, and he sees the whole world in terms of his weight"
(460). Adolescence may be the more delicate period for body image disorders (24) Thus, constrained by a myriad of social and subjective factors; receiving no solution to their despair; subjected to many clinical complications, the strong become indignant and decide that modern medicine is a fraud and their representatives are fools. The weak just give up the struggle. In
either case, the result is the same: further weight gain, resignation
to an abominable fate and a resolution to live a tolerable life during
the short span allotted to them - a fight for doctors and Insurance
Companies.
6)
Weight control programs: Why did we not reach our goal? Since no effective treatment has been found so far, several Investigators have recently adhered to the nihilistic hypothesis that "no treatment is much better that any treatment at all". In our opinion, we did not reach our goal because: •
For centuries, obesity has been considered a minor health problem and
has not been given proper attention by the Medical Community (179). As far as heredity is concerned, several studies on families from adopted children and twins, concluded that a predisposition to obesity may be genetically determined (14-202-508). Family studies reported that rough heredity estimates ranging from 0.40 to 0.60, suggest that genes are responsible for approximately one-half of the total phenotypic variation in obesity (454). However, both reports reflect only the common set of genes that influence obesity during the ages being considered, but do not reflect the impact of age-specific genetic effects. Thus, they may underestimate the total heredity of obesity at any given point in time (64-65). Despite the fact that genotype is determined by genes, phenotype ( the genotype related to external factors) can be a determinant factor in the genesis of obesity (61-75-462-505). Phenotype is strongly influenced by environmental factors (such as easy availability of refined foods), that can strongly influence the onset of the disorder. The obese phenotype is a multifactorial trait, determined by genetic and non-genetic factors. Among non-genetic factors, we could include total caloric intake, composition of the diet, psychological factors, and habit-modifications (quitting smoking, drinking, etc.) (63). It would be interesting, therefore, to consider two kinds of genetic effects: the additive effect of genetics and the result of the genotype-environment interaction. Genotype account for a significant fraction of the individual differences in Resting Metabolic Rate, Thermic Effect of Food (TEF) and Thermal Effect of Exercise (TEE) Genotype-environment interaction accounts for the rest in this equation. It
would be reasonable to suppose that, given a fixed percentage of hereditary
factors in the genesis of obesity, the environmental factors of contemporary
society play a key role in the ever increasing number of obese individuals
who live in industrialized nations (58-75-133-470).
The decrease in physical activity observed in obese individuals could be related to adiposity level. Basically, the process of becoming obese requires an over-consumption of food and some basic regulatory disorder, but once obesity is established, physical inactivity may contribute to aggravate the disease. That over-consumption of food is not the only cause for the genesis of obesity was clearly demonstrated in a series of research studies concluding that some volunteers maintained a fairly stable weight throughout the study, despite a food intake well over their daily requirement, whereas those prone to obesity gained weight (427) However,
physical exercise provides some benefits in the management of obesity.
Limits the amount of muscle tissue that is lost during a weight reduction
program; produces psychological benefits, including improvements in
mood and self-esteem, and prevents the urge to snack that is more prevalent
during periods of inactivity (120-379-414-466).
It is estimated that in the United States, about 300,000 deaths a year are caused directly or indirectly by obesity. The frequency of overweight appears to increase in frequency in the older population. Fifty two percent of American women and 42 percent of American men ages 50 to 59 are overweight, whereas the percentage for Americans between the ages of 20 to 29 is 20. But the young are hardly exempt: 25 percent of children between the ages of 6 and 17 are now obese according to any standard (180) Women have a higher tendency to be overweight and obese than men. The NHANES 11 survey concluded that 25.8 per cent of American women and 22.8 per cent of men are overweight, 24 percent of women and 22 percent of men are obese. Therefore, the prevalence of obesity among adult Americans appears alarmingly high. Men's and women's body weights have progressively increased between 1960 and 1980 (469). American adults have shown an average weight gain of nearly eight pounds per person, with 33.4 percent now considered obese, compared to 25.4 per cent in 1980 and 24.3 per cent in 1962 (469). Although
African American and Hispanic women remain the groups most prone to
obesity (48,6 and 46,7 per cent respectively), the largest increases
have been among white men and women: 7.8 percent and 9.1 percent respectively
are now more overweight than a decade ago. For example, the American food Industry generates 3,700 calories a day for every man, women and child and spends $ 36 billion a year to advertise its products (469).Up to 10,000 food commercials, specially designed for children, are displayed every year: Nearly all food ads on Saturday mornings are for sugary, fatty or salty foods (469). Concerning our tendency to inactivity, Kelly Brownell concluded: "the amount of energy that people used to expend even a decade ago is enormous compared to what they expend today" (258-469). While
an increase in physical activity does not contribute to further weight
loss, it elevates the body's aerobic capacity, increases the activity
of plasmatic neuropeptides which creates a sense of well-being, and
replaces body fat with muscle mass (which is lighter, but has better
aerobic turnover rate (74). Each contributes to or aggravates the condition and the condition becomes more or less severe, depending on the number of factors involved. Thus, male subjects with hereditary obesity traits, living in an industrialized country, subjected to different psychological pressures and displaying the abdominal type of body fat distribution, face greater health risks than female subjects, with no hereditary obesity traits, and a gynoid type of body fat distribution. As
per the following diagram, all these factors lead to the same conclusion:
They aggravate or generate a subtle modification at the hypothalamic
neurotransmitter level, which in turn initiates an amount of stored
fat greatly exceeding daily energy requirement.
15) The "villain" in our story: The hypothalamus as the end organ in the genesis of obesity.
For
those of us who refuse to be discouraged there is hope. Buried deep
in the human brain, there is a part that humans have in common with
all vertebrate animals, the diencephalon. It is a very primitive part
of the brain that, in humans, is buried under masses of nervous tissue
giving us the ability to think, reason and voluntarily move our body. It has been known that the destruction of another diencephalic center produces a voracious appetite and rapid weight gain in animals that never become fat spontaneously (Simeons, Pounds and Inches) (213-233). The hypothalamus is the most studied and best understood of all the Central Nervous System components regulating food intake and energy metabolism (70). It has long been recognized that it plays a key role in the mechanisms regulating food intake and fat accumulation (9-10-213-260-324-355-372-410-511). Electrical or chemical destruction of the hypothalamic region results in hyperphagia and obesity, or decreased hunger, depending on the anatomic area where damage has taken place (438-448-449). A laboratory lesion of the Ventromedial hypothalamus (VMH) results in hyperphagia, hyperinsulinemia, decreased GH secretion, rapid weight gain and obesity that persist until a new plateau in body weight is achieved. By contrast, verified cases of human hypothalamic obesity due to tumors, inflammations or injury due to surgery are extremely rare in the literature (71-101). Therefore, as we have proposed in a previous report, slight changes at the hypothalamic neurotransmitters level might account for the weight gain that obese patients experience despite continued efforts at dieting. In fact, some publications suggest that human obesity might be characterized by a subtle hypothalamic disorder, still not accessible to current diagnostic methods. Indirect evidence supporting this hypothesis can be presumed from several data: (36-169-410). Amatruda et al. demonstrated that a group of obese males showed an abnormal response to 100 g. of GnrH (Gonadotrophin Releasing Hormone), indicating a dysfunction of the hypothalamus (15). Jung et.al. concluded that women with hereditary obesity traits display a hypothalamic function disorder that is not totally corrected after weight loss (248). Kopelman et al., after investigating the Prolactin response to insulin-induced hypoglycemia, concluded that hypothalamic function is severely altered in human obesity (273-264). Although a hypothalamic regulation of energy metabolism might be crucial in the genesis of obesity, the food-intake regulatory process is a complex mechanism encompassing several CNS regions. Destruction of various components of the limbic system (temporal and frontal lobes for example) has been shown to cause obesity, although these are very rare situations. On the other hand, the hypothalamic region receives signals from different regions of the body. Many of these are mediated by neuropeptides (78-293-332). Regulation of eating behavior, including receipt of the signal to begin and stop eating, is facilitated by a series of gastrointestinal humor factors including Cholecystokinin, bombesin, vasoactive inhibitory peptide, pancreatic polypeptide and gastrin (437-491). The administration of Cholecystokinin has been shown to decrease food intake both in laboratory animals and humans (367). Parenteral administration of bombesin decreases eating in rats, an effect not eradicated by vagotomy (491). Regarding metabolic modifications observed in obesity, changes in the concentration of plasmatic hormones might also send different signals to the hypothalamic region. Thus, an intracranial administration of insulin to rats and baboons has been reported to decrease food intake. Hyperphagia and hyperinsulinemia appear to be two important factors in the development of hypothalamic obesity in experimental animals. The later (hyperinsulinemia) seems to be essential for the development of obesity in animals with a hypothalamic Ventromedial lesion (70). Since insulin is a lipogenic hormone, an increased plasmatic level of this substance might account for the excessive fat that has been observed to accumulate in cases of obesity. Substances such as norepinephrine, serotonin, Thyrotrophin Releasing Hormone, dopamine and neural peptides (b-endorphins, Cholecystokinin, dynorphin, enkephalins, bombesin, etc. act as intermediates in this complex network. These substances might play an important role also in the genesis of obesity: for example, several data suggest that a CNS opioid system regulates energy metabolism and ingestion of nutrients (204-270-308-310-311-313-409-515). ß-endorphin has been one of the most investigated neuropeptides (56-189-200-227-276-278-296-316-330-331-332-333-368-406-407-515) This molecule acts upon the mechanisms, eliciting eating through a food-rewarding system. For example, food ingestion might increase CNS opioids levels thus creating a feeling of self gratification. Obese subjects could, therefore, feel compelled to increase their food intake to maintain CNS an elevated neuropeptides concentration. Gluttony, as observed in obese patients, would consequently be biochemically explained. Food addiction may be a recognizable CNS opioid disorder (308). Gambert reported that fasting decreases the content of hypothalamic ß-endorphin in rats. Therefore, food restriction, as observed during dieting, might account for the feeling of weakness, hunger and physical distress associated with a low calorie diet (174). Finally, some evidence suggests that the diencephalic region plays a regulatory role on the mechanisms that are responsible for the storage and release of fat (98). Research on hypothalamic neuropeptides may shed new light on the interpretation of obesity, i.e., subtle biochemical modifications in the hypothalamic opioids concentration may be the cause (or the indication) of an underlying neuromodulator disorder (99-109-406). This would in turn initiate and perpetuate the metabolic changes leading to the obese condition (427). Conversely,
a persistent elevated food intake could lead to metabolic modifications
in the diencephalic region, as observed in obesity. These modifications
might be mediated by the Autonomic Nervous System (ANS), or the Endocrine
System (ES). One of the suspected glands was the thyroid, because it was observed that hypothyroid patients showed, among other physical signs, moderate degrees of obesity. However, recent research demonstrates that thyroid tests are within normal limits in the vast majority of obese patients. In the few cases where thyroid dysfunction appears to be associated with obesity, the condition may be easily corrected with the proper administration of thyroid hormones indicated for the management of hypothyroidism. Therefore, it would appear that thyroid dysfunction plays a minor (or null) role in obesity and only when it is not properly treated. Adrenal cortical hormones also have been associated with obesity. However, hypercorticism appears in a few cases of obesity, and nearly always in the context of an abdominal or android type of body fat distribution (402). Modifications of growth hormone (GH) secretion were observed in some obese patients (57-77-156). But it appears that this is a consequence rather than the cause of obesity. Reports were published regarding obesity treatment with Growth Hormone (92). This approach should be viewed with caution, since prolonged administration of GH may provoke the onset of a Parkinsonian syndrome (342-381). Furthermore, with a recent publication demonstrating an approximate 2-fold increase in mortality in critically ill patients receiving large doses of GH, the use of GH should remain in the realms of replacement therapy and research, until there are significant advances in our understanding. Gonadal steroids do not appear to play a role in the genesis of obesity. Rather, they are related to the peripheral conversion of estrogen and testosterone, since this conversion is carried out mainly in adipose tissue (375-377-378). Metabolic
gonadal steroids activity might account for the selective accumulation
of fat in certain regions, as observed in gynoid (Estrogen), or android
(Testosterone) obesity. After many years of experience on the subject and a careful review of all the information previously cited, I have concluded that this belief, reasonable as it may seem, is not the complete solution to the disorder. First, several reported studies conclude that weight regain after dieting was the rule rather than the exception. Next, it has been repeatedly demonstrated that, under very controlled conditions (same Hypercaloric Diet), some subjects failed to loose weight, or reported their weight remained stable despite broad changes in their food intake, and, Some obese patients failed to lose weight despite following a strictly controlled diet. No patient is so enthusiastic as an overweight patient who is anxious to lose those unwanted pounds. While some patients are grossly obese, the vast majority of these present a moderate overweight. The former are case problems for General surgeons (gastric bandage, etc.), since the disease usually recurs or aggravates throughout the years. Patients should discuss the problem of obesity with their physicians. Both need to understand what they are facing is a chronic problem like diabetes or hypertension, that ranges from moderate to severe, and they must treat the disease as a serious health hazard. In any case, a pre-surgical weight management program is likely to yield better results, both from the patient's and surgeon’s viewpoint. |
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