Obesity
Body fat percentage, body mass index, skin thicknesses, and anthropomorphic measures
Obesity represents a state of excess storage of body fat. Although similar, the term overweight is puristically defined as an excess
body weight for height. Although men have a body fat percentage of 15-20%, women have approximately 25-30%. Because
differences in weight among individuals are only partly due to variations in body fat, body weight is a limited, though easily obtained,
index of obesity.
The body mass index (BMI), also known as the Quetelet index, is used far more commonly than body fat percentage to define
obesity. BMI is closely correlated with the degree of body fat in most settings. BMI = weight/height2, where weight is in kilograms and
height is in meters.
The body fat percentage can be estimated by using the Deurenberg equation, as follows: body fat percentage = 1.2(BMI) + 0.23(age)
- 10.8(sex) - 5.4, where age is in years and sex is 1 for male and 0 for female. This equation has a standard error of 4% and
accounts for approximately 80% of the variation in body fat.
Although the BMI is typically closely correlated with percentage body fat in a curvilinear fashion, some important caveats to its
interpretation apply. In mesomorphic (muscular) persons, BMIs that usually indicate overweight or mild obesity may be spurious,
whereas in some persons with sarcopenia (especially among persons of Asian descent), a typically normal BMI may conceal
underlying excess adiposity characterized by increased percentage fat mass and reduced muscle mass.
In view of these limitations, some authorities advocate a definition of obesity based on percentage body fat. For men, percentage
body fat greater than 25% defines obesity, and 21-25% is borderline. For women, over 33% defines obesity, and 31-33% is
borderline.
Other indices used to estimate the degree and distribution of obesity include the 4 standard skin thicknesses (ie, subscapular,
triceps, biceps, suprailiac) and various anthropometric measures, of which waist and hip circumferences are the most important.
Classifications and definitions of obesity
Although several classifications and definitions for degrees of obesity are accepted, the most widely accepted is the World Health
Organization (WHO) criteria based on BMI. Under this convention for adults, grade 1 overweight (commonly and simply called
overweight) is a BMI of 25-29.9 kg/m2. Grade 2 overweight (commonly called obesity) is a BMI of 30-39.9 kg/m2. Grade 3 overweight
(commonly called severe or morbid obesity) is a BMI greater than or equal to 40 kg/m2.
The surgical literature often uses a different classification to recognize particularly severe obesity. In this setting, a BMI greater than
40 kg/m2 is described as severe obesity, a BMI of 40-50 kg/m2 is termed morbid obesity, and a BMI greater than 50 kg/m2 is termed
super obese.
The definition of obesity in children involves BMIs greater than the 85th (commonly used to define overweight) or the 95th (commonly
used to define obesity) percentile, respectively, for age-matched and sex-matched control subjects.
Comorbidities associated with obesity
Apart from total body fat mass, accumulating data suggest that regional fat distribution substantially affects the incidence of
comorbidities associated with obesity. High abdominal fat content (including visceral and, to a lesser extent, subcutaneous
abdominal fat) is strongly correlated with worsened metabolic and clinical consequences of obesity. As a result, android obesity,
which is predominantly abdominal, is more predictive of adipose-related comorbidities than gynecoid obesity, which has a relatively
peripheral (gluteal) distribution.
Waist circumferences greater than 94 cm in men and greater than 80 cm in women and waist-to-hip ratios greater than 0.95 in men
and greater than 0.8 in women are the thresholds for significantly increased potential cardiovascular risk. Circumferences of 102 cm
in men and 88 cm in women indicate a markedly increased potential risk requiring urgent therapeutic intervention; these are the
thresholds used in the Adult Treatment Panel III (ATPIII) definition of the metabolic syndrome.
Obesity is associated with a host of potential comorbidities that significantly increase the potential morbidity and mortality
associated with the condition. Although no cause-and-effect relationship is exhaustively demonstrated for all these comorbidities,
amelioration of these conditions after substantial weight loss suggests that obesity probably plays an important role in their
development.
Relevant anatomy and areas of research
The adipocyte, which is the cellular basis for obesity, is increasingly found to be a complex and metabolically active cell. At present,
the adipocyte is being perceived as an endocrine gland with several peptides and metabolites that may be relevant to the control of
body weight, and these are being studied intensively. Among the products of the adipocyte involved in complex intermediary
metabolism are cytokines, tumor necrosis factor-alpha, interleukin-6, lipotransin, adipocyte lipid-binding protein, acyl-stimulation
protein, prostaglandins, adipsin, perilipins, lactate, adiponectin, monobutyrin, and phospholipid transfer protein.
Among critical enzymes involved in adipocyte metabolism are endothelial derived lipoprotein lipase (lipid storage), hormone-
sensitive lipase (lipid elaboration and release from adipocyte depots), acylcoenzyme A (acyl-CoA) synthetases (fatty acid synthesis),
and a cascade of enzymes (beta oxidation and fatty acid metabolism). The ongoing flurry of investigation into the intricacies of
adipocyte metabolism in the last 5 years not only improved our understanding of the pathogenesis of obesity but also offered several
potential targets for therapy.
Another area of active research is investigation of the cues for the differentiation of preadipocytes to adipocytes. With the fairly recent
recognition that this process occurs in both white and brown adipose tissue, even in adults, its potential role in the development of
obesity and the relapse to obesity after weight loss has become more important than before. Among the identified factors in this
process are transcription factors peroxisome proliferator-activated receptors-gamma (PPAR-gamma); retinoid-X receptor ligands;
perilipin; adipocyte differentiation-related protein (ADRP); and CCAAT enhancer-binding proteins (C/EBP) alpha, beta, and delta.
Pathophysiology
The pathogenesis of obesity is far more complex than the simple paradigm of an imbalance between energy intake and energy
output. Although this concept allows easy conceptualization of the various mechanisms involved in the development of obesity,
obesity is far more than the mere result of too much eating and/or too little exercise. However, the prevalence of inactivity in
developed countries is considerable and relevant. In the United States, only approximately 22% of adults and 25% of adolescents
report notable regular physical activity. Approximately 25% of adults in the United States report no remarkable physical activity during
leisure, while approximately 14% of adolescents have similar reports of inactivity.
Two major groups of factors with a balance that variably intertwines in the development of obesity are genetics, which is presumed
to explain 40-70% of the variance in obesity, and environmental factors. Although the high prevalence of obesity in the children of
parents who are obese and the high concordance of obesity in identical twins suggest a substantial genetic component to the
pathogenesis of obesity, the secular trends of the last few decades, which are coincident with recent changes in dietary habits and
activity, also suggest an important role for environmental factors.
Leptin
Friedman et al discovered leptin (from the Greek word leptos, meaning thin) in 1994 and ushered in an explosion of research and a
great increase in knowledge about regulation of the human feeding and satiation cycle. Since this discovery, neuromodulation of
satiety and hunger with feeding has been found to be far more complex than the old simplistic model of the ventromedial
hypothalamic nucleus and limbic centers of satiety and the feeding centers of the lateral hypothalamus. Leptin is a 16-kD protein
produced predominantly in white adipose tissue and, to a lesser extent, in the placenta, skeletal muscle, and stomach fundus in
rats. Leptin has a myriad of functions in carbohydrate, bone, and reproductive metabolism that are still being unraveled, but its role in
body weight regulation is the main reason it came to prominence.
The major role of leptin in body-weight regulation is to signal satiety to the hypothalamus and, thus, reduce dietary intake and fat
storage while modulating energy expenditure and carbohydrate metabolism to prevent further weight gain. Unlike the Ob/Ob mouse
model in which this peptide was first characterized, most humans who are obese are not leptin deficient but rather leptin resistant.
Therefore, they have elevated circulating levels of leptin. Although more than 90% of human cases of obesity are polygenic, the
recognition of monogenic variants has greatly enhanced our knowledge about the etiopathogenesis of obesity.
Monogenic models for obesity in humans and experimental animals
Various monogenic models have greatly increased our knowledge about mechanisms of obesity, and they have provided several
potential targets for future antiobesity medications.
Proopiomelanocortin (POMC) and alpha–melanocyte-stimulating hormone (alpha-MSH) both act centrally on the melanocortin
receptor 4 (MC 4) to reduce dietary intake. Genetic defects in POMC production and mutations in the MC4 gene are described as
monogenic causes of obesity in humans. Of particular interest is that patients with POMC mutations, tend to have red hair because
of the resultant deficiency in MSH production. Also, because of their diminished levels of adrenocorticotropic hormone (ACTH), they
tend to have central adrenal insufficiency. Recent data suggest that as many as 5% of children who are obese have MC4 or POMC
mutations. If confirmed, these would be the most common identifiable genetic defects associated with obesity in humans (band
2p23 for POMC and band 18q21.3 for MC4).
Ob/Ob mice were the prototypical mice that enabled the discovery of leptin. These mice lack the leptin gene and are overweight and
hyperphagic. A few humans with a similar genetic defect and similar phenotypic consequences have been identified. This variant of
obesity, though minor in the grand scheme of human obesity, is exquisitely sensitive to leptin injection, with reduced dietary intake
and profound weight loss. (The involved band is at 7q31.)
Db/Db mice have mutations of the leptin receptor in the hypothalamus. Fa/Fa mice also have leptin-receptor mutations. These mice
have early-onset obesity and hyperphagia like the Ob/Ob mice, but they also have normal or elevated leptin levels. Human
counterparts of this model are rare; their conditions are associated with hyperphagia, hypogonadotrophic hypogonadism, and
defective thyrotropin secretion but not associated with hypercortisolism, hyperglycemia, and hypothermia, as occurs in Db/Db mice
(involvement at band 1p31). The leptin receptor is one of the cytokine receptor families of receptors and is activated through the
Janus kinases/signal transducers and activators of transcription (JAK/STAT) mechanisms.
Prohormone convertase is an enzyme that is critical in protein processing, and it appears to be involved in the conversion of POMC
to alpha-MSH. Rare patients identified to have alterations in this enzyme have clinically significant obesity, hypogonadotrophic
hypogonadism, and central adrenal insufficiency. This is one of the few models of obesity not associated with insulin resistance.
(The involved band is 5q15-21.)
PPAR-gamma is a transcription factor that is involved in adipocyte differentiation. All humans with mutations of the receptor (at band
3p25) described so far have severe obesity.
In addition to the monogenic models of obesity mentioned above, genome-wide linkage analyses and microarray technology have
revealed a rapidly growing list of potential susceptibility obesity genes. Among those identified that are being actively studied are
genes on chromosome arms 2p, 10p, 5p, 11q, and 20q.
In the same line as the evidence that proved Helicobacter pylori as the cause for peptic ulcer disease, evolving data suggest that a
notable inflammatory and possibly infective etiology may exist for obesity. Adipose tissue is known to be a repository of various
cytokines, especially interleukin-6 and tumor necrosis factor-alpha.
Data have shown that adenovirus 36 infection is associated with obesity in chickens and mice. Other data suggest that, though
humans who are not obese have a 5% prevalence of adenovirus 36 infection, humans who are obese have a prevalence of 20-30%.
Body fat percentage, body mass index, skin thicknesses, and anthropomorphic measures
Obesity represents a state of excess storage of body fat. Although similar, the term overweight is puristically defined as an excess
body weight for height. Although men have a body fat percentage of 15-20%, women have approximately 25-30%. Because
differences in weight among individuals are only partly due to variations in body fat, body weight is a limited, though easily obtained,
index of obesity.
The body mass index (BMI), also known as the Quetelet index, is used far more commonly than body fat percentage to define
obesity. BMI is closely correlated with the degree of body fat in most settings. BMI = weight/height2, where weight is in kilograms and
height is in meters.
The body fat percentage can be estimated by using the Deurenberg equation, as follows: body fat percentage = 1.2(BMI) + 0.23(age)
- 10.8(sex) - 5.4, where age is in years and sex is 1 for male and 0 for female. This equation has a standard error of 4% and
accounts for approximately 80% of the variation in body fat.
Although the BMI is typically closely correlated with percentage body fat in a curvilinear fashion, some important caveats to its
interpretation apply. In mesomorphic (muscular) persons, BMIs that usually indicate overweight or mild obesity may be spurious,
whereas in some persons with sarcopenia (especially among persons of Asian descent), a typically normal BMI may conceal
underlying excess adiposity characterized by increased percentage fat mass and reduced muscle mass.
In view of these limitations, some authorities advocate a definition of obesity based on percentage body fat. For men, percentage
body fat greater than 25% defines obesity, and 21-25% is borderline. For women, over 33% defines obesity, and 31-33% is
borderline.
Other indices used to estimate the degree and distribution of obesity include the 4 standard skin thicknesses (ie, subscapular,
triceps, biceps, suprailiac) and various anthropometric measures, of which waist and hip circumferences are the most important.
Classifications and definitions of obesity
Although several classifications and definitions for degrees of obesity are accepted, the most widely accepted is the World Health
Organization (WHO) criteria based on BMI. Under this convention for adults, grade 1 overweight (commonly and simply called
overweight) is a BMI of 25-29.9 kg/m2. Grade 2 overweight (commonly called obesity) is a BMI of 30-39.9 kg/m2. Grade 3 overweight
(commonly called severe or morbid obesity) is a BMI greater than or equal to 40 kg/m2.
The surgical literature often uses a different classification to recognize particularly severe obesity. In this setting, a BMI greater than
40 kg/m2 is described as severe obesity, a BMI of 40-50 kg/m2 is termed morbid obesity, and a BMI greater than 50 kg/m2 is termed
super obese.
The definition of obesity in children involves BMIs greater than the 85th (commonly used to define overweight) or the 95th (commonly
used to define obesity) percentile, respectively, for age-matched and sex-matched control subjects.
Comorbidities associated with obesity
Apart from total body fat mass, accumulating data suggest that regional fat distribution substantially affects the incidence of
comorbidities associated with obesity. High abdominal fat content (including visceral and, to a lesser extent, subcutaneous
abdominal fat) is strongly correlated with worsened metabolic and clinical consequences of obesity. As a result, android obesity,
which is predominantly abdominal, is more predictive of adipose-related comorbidities than gynecoid obesity, which has a relatively
peripheral (gluteal) distribution.
Waist circumferences greater than 94 cm in men and greater than 80 cm in women and waist-to-hip ratios greater than 0.95 in men
and greater than 0.8 in women are the thresholds for significantly increased potential cardiovascular risk. Circumferences of 102 cm
in men and 88 cm in women indicate a markedly increased potential risk requiring urgent therapeutic intervention; these are the
thresholds used in the Adult Treatment Panel III (ATPIII) definition of the metabolic syndrome.
Obesity is associated with a host of potential comorbidities that significantly increase the potential morbidity and mortality
associated with the condition. Although no cause-and-effect relationship is exhaustively demonstrated for all these comorbidities,
amelioration of these conditions after substantial weight loss suggests that obesity probably plays an important role in their
development.
Relevant anatomy and areas of research
The adipocyte, which is the cellular basis for obesity, is increasingly found to be a complex and metabolically active cell. At present,
the adipocyte is being perceived as an endocrine gland with several peptides and metabolites that may be relevant to the control of
body weight, and these are being studied intensively. Among the products of the adipocyte involved in complex intermediary
metabolism are cytokines, tumor necrosis factor-alpha, interleukin-6, lipotransin, adipocyte lipid-binding protein, acyl-stimulation
protein, prostaglandins, adipsin, perilipins, lactate, adiponectin, monobutyrin, and phospholipid transfer protein.
Among critical enzymes involved in adipocyte metabolism are endothelial derived lipoprotein lipase (lipid storage), hormone-
sensitive lipase (lipid elaboration and release from adipocyte depots), acylcoenzyme A (acyl-CoA) synthetases (fatty acid synthesis),
and a cascade of enzymes (beta oxidation and fatty acid metabolism). The ongoing flurry of investigation into the intricacies of
adipocyte metabolism in the last 5 years not only improved our understanding of the pathogenesis of obesity but also offered several
potential targets for therapy.
Another area of active research is investigation of the cues for the differentiation of preadipocytes to adipocytes. With the fairly recent
recognition that this process occurs in both white and brown adipose tissue, even in adults, its potential role in the development of
obesity and the relapse to obesity after weight loss has become more important than before. Among the identified factors in this
process are transcription factors peroxisome proliferator-activated receptors-gamma (PPAR-gamma); retinoid-X receptor ligands;
perilipin; adipocyte differentiation-related protein (ADRP); and CCAAT enhancer-binding proteins (C/EBP) alpha, beta, and delta.
Pathophysiology
The pathogenesis of obesity is far more complex than the simple paradigm of an imbalance between energy intake and energy
output. Although this concept allows easy conceptualization of the various mechanisms involved in the development of obesity,
obesity is far more than the mere result of too much eating and/or too little exercise. However, the prevalence of inactivity in
developed countries is considerable and relevant. In the United States, only approximately 22% of adults and 25% of adolescents
report notable regular physical activity. Approximately 25% of adults in the United States report no remarkable physical activity during
leisure, while approximately 14% of adolescents have similar reports of inactivity.
Two major groups of factors with a balance that variably intertwines in the development of obesity are genetics, which is presumed
to explain 40-70% of the variance in obesity, and environmental factors. Although the high prevalence of obesity in the children of
parents who are obese and the high concordance of obesity in identical twins suggest a substantial genetic component to the
pathogenesis of obesity, the secular trends of the last few decades, which are coincident with recent changes in dietary habits and
activity, also suggest an important role for environmental factors.
Leptin
Friedman et al discovered leptin (from the Greek word leptos, meaning thin) in 1994 and ushered in an explosion of research and a
great increase in knowledge about regulation of the human feeding and satiation cycle. Since this discovery, neuromodulation of
satiety and hunger with feeding has been found to be far more complex than the old simplistic model of the ventromedial
hypothalamic nucleus and limbic centers of satiety and the feeding centers of the lateral hypothalamus. Leptin is a 16-kD protein
produced predominantly in white adipose tissue and, to a lesser extent, in the placenta, skeletal muscle, and stomach fundus in
rats. Leptin has a myriad of functions in carbohydrate, bone, and reproductive metabolism that are still being unraveled, but its role in
body weight regulation is the main reason it came to prominence.
The major role of leptin in body-weight regulation is to signal satiety to the hypothalamus and, thus, reduce dietary intake and fat
storage while modulating energy expenditure and carbohydrate metabolism to prevent further weight gain. Unlike the Ob/Ob mouse
model in which this peptide was first characterized, most humans who are obese are not leptin deficient but rather leptin resistant.
Therefore, they have elevated circulating levels of leptin. Although more than 90% of human cases of obesity are polygenic, the
recognition of monogenic variants has greatly enhanced our knowledge about the etiopathogenesis of obesity.
Monogenic models for obesity in humans and experimental animals
Various monogenic models have greatly increased our knowledge about mechanisms of obesity, and they have provided several
potential targets for future antiobesity medications.
Proopiomelanocortin (POMC) and alpha–melanocyte-stimulating hormone (alpha-MSH) both act centrally on the melanocortin
receptor 4 (MC 4) to reduce dietary intake. Genetic defects in POMC production and mutations in the MC4 gene are described as
monogenic causes of obesity in humans. Of particular interest is that patients with POMC mutations, tend to have red hair because
of the resultant deficiency in MSH production. Also, because of their diminished levels of adrenocorticotropic hormone (ACTH), they
tend to have central adrenal insufficiency. Recent data suggest that as many as 5% of children who are obese have MC4 or POMC
mutations. If confirmed, these would be the most common identifiable genetic defects associated with obesity in humans (band
2p23 for POMC and band 18q21.3 for MC4).
Ob/Ob mice were the prototypical mice that enabled the discovery of leptin. These mice lack the leptin gene and are overweight and
hyperphagic. A few humans with a similar genetic defect and similar phenotypic consequences have been identified. This variant of
obesity, though minor in the grand scheme of human obesity, is exquisitely sensitive to leptin injection, with reduced dietary intake
and profound weight loss. (The involved band is at 7q31.)
Db/Db mice have mutations of the leptin receptor in the hypothalamus. Fa/Fa mice also have leptin-receptor mutations. These mice
have early-onset obesity and hyperphagia like the Ob/Ob mice, but they also have normal or elevated leptin levels. Human
counterparts of this model are rare; their conditions are associated with hyperphagia, hypogonadotrophic hypogonadism, and
defective thyrotropin secretion but not associated with hypercortisolism, hyperglycemia, and hypothermia, as occurs in Db/Db mice
(involvement at band 1p31). The leptin receptor is one of the cytokine receptor families of receptors and is activated through the
Janus kinases/signal transducers and activators of transcription (JAK/STAT) mechanisms.
Prohormone convertase is an enzyme that is critical in protein processing, and it appears to be involved in the conversion of POMC
to alpha-MSH. Rare patients identified to have alterations in this enzyme have clinically significant obesity, hypogonadotrophic
hypogonadism, and central adrenal insufficiency. This is one of the few models of obesity not associated with insulin resistance.
(The involved band is 5q15-21.)
PPAR-gamma is a transcription factor that is involved in adipocyte differentiation. All humans with mutations of the receptor (at band
3p25) described so far have severe obesity.
In addition to the monogenic models of obesity mentioned above, genome-wide linkage analyses and microarray technology have
revealed a rapidly growing list of potential susceptibility obesity genes. Among those identified that are being actively studied are
genes on chromosome arms 2p, 10p, 5p, 11q, and 20q.
In the same line as the evidence that proved Helicobacter pylori as the cause for peptic ulcer disease, evolving data suggest that a
notable inflammatory and possibly infective etiology may exist for obesity. Adipose tissue is known to be a repository of various
cytokines, especially interleukin-6 and tumor necrosis factor-alpha.
Data have shown that adenovirus 36 infection is associated with obesity in chickens and mice. Other data suggest that, though
humans who are not obese have a 5% prevalence of adenovirus 36 infection, humans who are obese have a prevalence of 20-30%.
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- More about Obesity
Classification of Obesity
Basic Methods for
Measurement of Obesity
Epidemiology of Obesity
Etiology of Obesity
Behavioral Change
Proactol
Lipocerin
Chitosan
Biosculpt Night
Time Weight
Loss Formula
Conjugated
linoleic acid
(CLA)
Pyruvate
Lipocerin
Chitosan
Biosculpt Night
Time Weight
Loss Formula
Conjugated
linoleic acid
(CLA)
Pyruvate
Fat Burn