Obesity is excess body fat frequently resulting in a significant impairment of health.
Body fat is comprised of triglycerides and steroids. Triglycerides and phospholipids are included in the fats & fatty acid category whereas hormones and cholesterol are found in the steroid category.
Triglycerides are made up of a glycerol molecule (green) and three fatty acids. The fatty acids can be
unsaturated (double bonds)
The unsaturated double bond can be either cis or trans. The trans bond is considered carcinogenic.
Triglycerides are the main form of lipid storage.
Common Fatty Acids
The phospholipid is a modification of the triglyceride. Instead of three fatty acids, the phospholipid contains two fatty acids and one phosphate - complex attached to the glycerol molecule. Other molecules are attached to the phosphate molecule forming different types of phospholipids.
Phospholipids are the primary component of cell membranes.
Steroids are composed of several six carbon rings.
Reproductive hormones, metabolic & immune substances, and cholesterols are steroids.
Lipid, specifically triglycerides, is stored for fuel as well as a lipid bank for the other function of lipids.
Cell membrane Structure
Hormones and Other Mediators
As a fuel, free fatty acids have the densest caloric content. The caloric value of fats is 9.0 kcal/gram where as carbohydrates and proteins are 4.0 kcal/gram. Approximately 90% of the adipocyte is triglyceride storage. The adipocyte can be found in separate and isolated fat deposits or intra-organ fat deposits.
Phospholipid is the primary lipid in the cell membrane of every cell. The phospholipids are arranged in a bi layer with the hydrophilic head facing the extracellular fluid and the cytoplasm.
This hydrophilic head is the layer that prevents the cell from being dissolved in fluid.
Cholesterol is also an essential component of the cell membrane. Cholesterol modulates the fluidity of the cell membrane.
Hormones and other mediators are comprised mainly of steroids.
Reproductive hormones include
Other mediators include
Corticosteroids - stress hormones
Glucocorticoids - metabolism and immune function
Mineralocorticoids - fluid and electrolyte balance
Vitamins E, D, A & K are stored in the adipocyte.
Although not the primary function of fat deposits, insulation and organ protection is secondary.
In 1994, Leptin was found to originate from the adipocyte. Since then, over three dozen biochemical products are secreted by the adipocyte. Each of these endocrine factors may be characteristic of different fat deposits.
Endocrine function of the adipocyte can be divided into proteins and enzymes involved in steroid metabolism.
The adipocyte-derived proteins with endocrine function are summarized in the figure to the left. Each of these substances will be discussed below.
Similarly, the adipocyte expresses receptors for endocrine substances.
With the combination of specific receptors and production of endocrine and steriodogenic enzymes, the adipocyte performs specific functions in metabolism.
Different adipose deposits may function differently as to substances produced and affect on various tissue. For example, leptin is produced more in the subcutaneous fat than in the visceral fat; whereas, IL-6 is produced more in the visceral fat than in the subcutaneous.
In addition, the location of the adipose deposition exhibits different metabolic effects. Visceral adipose tissue secretes endocrine substances into the portal system providing direct access to the liver; whereas subcutaneous adipose secretes substances directly into the systemic circulation.
Similarly, the various adipose deposits also exhibit different receptor patterns. AT1, Beta3, glucocorticoid, and androgen receptors are more prevalent in visceral fat.
Leptin is found more in subcutaneous than visceral fat. Leptin is stimulated by the factors listed in green and inhibited by those listed in red.
The primary function of leptin is to increase satiety and energy expenditure through action on the hypothalamus.
In the muscle, leptin action increases glucose uptake and glucose metabolism. In the liver, leptin increases glucose production.
In the pancreases, leptin increases insulin. Leptin activates the hypothalamic-pituitary-adrenal axis; whereas it suppresses the hypothalamic-pituitary - thyroid axis and the hypothalamic -pituitary-gonadal axis.
MACROPHAGE & MONOCYTE CHEMOATTRACTANT PROTEIN-1
The adipocyte attracts macrophage activity. The primary action of the MPC-1 is to activate the immune activities of the macrophage; including secretion of TNF alpha and IL-6.
This increased MPC activity is also associated with insulin resistance in the adipocyte and inhibition of adipocyte growth.
TUMOR NECROSIS FACTOR alpha
TNF alpha is secreted more from the subcutaneous adipose deposits than from the visceral deposits and may be dependent on regional fat mass. Macrophage infiltration is associated with higher TNF alpha.
The primary action of TNF alpha is to increase insulin resistance in liver, muscle and adipose tissue.
Additional action on the liver include
increased free fatty acid (FFA) production and cholesterol synthesis and decreased glucose uptake and FFA storage.
INTERLEUKIN - 6
IL-6 is found more in visceral adipose deposits than in subcutaneous deposits. Macrophage infiltration increases IL-6 in adipose tissue. Approximately 1/3rd of the circulating IL-6 originates from the adipose tissue.
IL-6 primary function is to increase insulin resistance at the insulin receptor or insulin signaling pathway in hepatic, muscle and adipose tissue.
In addition, IL-6 increases hepatic hyperlipidemia and glucose production. In the central nervous system, IL-6 deficiency decreases energy expenditure.
PLASMINOGEN ACTIVATOR INHIBITOR - 1
PAI-1 is found more in visceral adipose deposits than in subcutaneous deposits.
Fibrinolysis the breaking down of blood clots. PAI-1 inhibits tissue plasminogen activator which initiates the fibrinolysis cascade. Thus, PAI-1 inhibits fibrinolysis.
TNF alpha increases PAI-1 in adipose tissue.
Adiponectin is found more in the subcutaneous adipose deposits than in the visceral deposits.
In the vasculature, adiponectin acts through the insulin receptor to increase nitric oxide (NO); which increases the anti-atherogenic activities of the endothelium.
In the liver, adiponectin decreases glucose production and FFA synthesis. In the muscle, adiponectin increases FFA oxidation and decreases triglyceride production.
Adipsin is found more in the subcutaneous adipose deposits than in the visceral deposits. Adipsin is the enzyme required for the production of Acylation Stimulating Protein (ASP).
Once converted, ASP increases insulin secretion. In the adipose tissue, ASP increases glucose transport, and triglyceride synthesis; and decreases lipolysis and FFA release.
Resistin is 15 times greater in the visceral adipose deposits than in the subcutaneous deposits.
The primary function of resistin is an increase in insulin resistance.
PROTEINS FROM THE RENIN ANGIOTENSIN SYSTEM (RAS)
RAS proteins are found more in visceral adipose deposits than subcutaneous deposits. RAS proteins include:
angiotensin converting enzyme
Similar to the renin-angiotensin system in the kidney, these proteins affect the same target organs. In the adrenal gland, aldosterone is increased, increasing the reabsorption of sodium and water in the kidneys. In the vasculature, vasoconstriction is primary activity from adipocyte RAS. In the liver, RAS results in decreased lipolysis with increased lipogenesis, gluconeogenesis, glycogenolysis, and insulin resistance.
Several enzymes from the adipose tissue are involved in steroid metabolism; activation, interconversion and inactivation.
The steroid activity can be divided into sex steroids and glucocorticoid activity.
For the most part, the enzymes involved in sex steroids convert androgens to estrogens. More specifically, they also convert specific sex steroids to their more active form; that is, androstenedione to testosterone and estrone to estrodiol.
In glucocorticoid activity, steroidgenic enzymes increase insulin sensitivity and control visceral adipose tissue deposition.
Fat cells are not all the same. Fat cells can vary in size from 20 to 200 micro m. The smallest fat cells can be found in the abdominal deposits whereas the largest fat cells can be found in the gluteal deposits. These different fat cells also exhibit variations in fat metabolism.
Adipose tissue can be classified many ways:
Fat can be divided into brown fat and white fat. Brown fat is thermogenic whereas white fat is primarily for storage.In humans, brown fat is only present in new born infants (5% brown fat).
Adipose deposits can be
Adipose deposits can be sex specific. In general, men deposit adipose on the trunk whereas women on the limbs.
Premenopausal women distribute more on the limbs, but redistribute to abdominal fat after menopause.
Visceral fat is internal abdominal fat in contrast to subcutaneous abdominal fat. Visceral fat is located inside the peritoneal cavity, packed in between internal organs.
Subcutaneous fat is found under the layer of skin.
Classification systems of obesity have also been based on phenotype, fat cell morphology, and health status.
Type I: Excess body mass or percentage fat
Type II: Excess subcutaneous truncal-abdominal fat (android)
Type III: Excess abdominal visceral fat
Type IV: Excess gluteal-femoral fat (gynoid)
an increase in fat cell number
an increase in fat cell size
Contributes to juvenile onset obesity
Contributes to adult onset obesity
Critical times for fat cell number to increase are:
last trimester of mother's pregnancy
first year of life
Fat cell size increases when fat storage exceeds fat release.
80% with hyperplastic obesity have difficulties reducing excess body fat because the fat cells are increased in number rather than in size. The number of fat cells can never be reduced.
Hyperplastic obesity can reduce easily because fat cell size reduces better than fat cell number.
Obesity is excess body fat frequently resulting in a significant impairment of health.
Obesity has been classified many ways. The most common classification systems have been height/weight tables, body mass index (BMI), and body fat percentage. More recently, an estimate of the distribution of body fat have been included in the assessment of body fat.
Height/Weight Tables: People are considered obese when they weigh more than twenty percent of their desirable weight as listed in the tables.
Body Mass Index: Although different BMI standards have been published for increased risk of disease for men [>27.8 kg/m2 ] and women [27.3 kg/m2 ], a combined categorization has been derived from the epidemiological literature:
Acceptable range (low risk)
BMI = body weight [kg]/height [m]2
Body Fat Distribution
The distribution of body fat is probably the most important factor in health and disease. The three types of fat distribution include:
An excess deposition of adipose tissue focused ont he trunk is Upper Body Obesity or Andriod Obesity. Upper body obesity, more specifically, visceral body fat distribution is related to disease etiologies.
An excess of deposition on the limbs or buttox is Lower Body Obesity or Gynoid Obesity.
Waist to Hip Ratio is considered a simple estimate of upper or lower body fat distribution. On the other hand, we found 29 different
anthropometric methods to determine wasit to hip ratio. In fact, the iliac crest was used as the waist measurement in some methods, but the him measurement in others.
We obtained circumferences from three sites (wasist, iliac crest, and hips) which varied among the 29 different methods and compared the variation in uppper and lower body fat categorization in 119 obese women and 81 obese men (hydrostatic weighing).
The percent of the population classified as upper or lower depended on the method used.
Wallace, J.P. P.G. Bogle, K.T. Murray, and W.C. Miller. Variation in the anthropometric dimensions for estimating upper and lower body obesity. Am Journal of Human Biology 6:699-709, 1994.
Standards for the method using
Waist - Minimal girth between the sternum & iliac crest
Hips - Maximal girth around the buttox
are summarized to the right.
Upper Body Obesity
Lower Body Obesity
Body Mass Index and Waist Circumference
The federal government has created the following classification system for body fat:
Increased Relative Risk to Normal Weight and Waist Circumference
25.0 - 29.9
30.0 - 34.9
35.0 - 39.9
Extreme Obesity III
Percent Body Fat
Percent body fat classifications can be based on athletic performance or health. These are based on health:
The first question to address in the etiology of overweight and obesity is the influences of genetics vs. environment.
Genetic Evidence - Evidence for genetic influences in body fat and body fat distribution can be supported by:
There are sex specific fat deposits that are associated with the inheritance of being male or female. Men have a tendency to have larger fat deposits on the trunk whereas women tend to have larger fat deposits on limbs.
Specific fat deposits have characteristic fat cell size and number. Visceral fat deposits contain the smallest fat cells whereas gluteal fat deposits contain the largest fat cells.
Science has created genetic strains of obese rats. The Zucker rat is the most well known genetic strain of fat rats
There are several human genetic diseases that are characterized by obesity
Bardet-Biedl Syndrome (BBS) exhibits the main features RP (rod-cone dystrophy), obesity, postaxial polydactyly, learning disabilities and hypogenitalism (males).
Prader- Willi Syndrome - characterized by poor muscle tone, low levels of sex hormones and a constant feeling of hunger.
Morgani-Stewart-Morel Syndrome - Thickening of the inner table of the frontal bone, which may be associated with hypertrichosis and obesity. It most commonly affects women near menopause.
Familial Weight Differences - are not significantly different between siblings or twins who live together or are separated early in life. In fact, adopted children exhibit better correlations with their biological parent (boys= 0.592 and girls = 0.340) than with their adoptive parents (boys = 0.113 and girls = 0.157).
In addition, the probabilities of lean/obese parents having lean/obese children are:
Lean x Lean
Lean x Obese
Obese x Obese
Ironically, we can replace the "child" in the above table with family dog or cat and get the same results. That is, two lean owners have a 90% chance of raising a lean dog or cat. The question then arises, does this table truly represent genetics or environment?
Experimental obesity studies offer the support for the interaction of genetics vs. environment.
Sims and colleagues have a classic study (Vermont Study) where students and prisoners overate to become obese (experimental obesity). They had to ingest 6700 to 10,000 kcal/day. Within 3-5 months, most of them reached the "obesity" criterion of 25% fat. However, the prisoners with the ectomorph body type never became obese. Those who became obese exited many characteristics of obese populations:
Five inmates of the Vermont State Prison volunteered to consume extra food for four months to become obese. They consumed 6700 to 10,000 calories per day. The mean percent body fat increased from 14.2% to 26.2 %. Yet, two subjects did not exceed 19.0% or 21.2% body fat respectively.
Bouchard conducted studies where 12 pair of identical twins overweight 1000 kcal/ day for 100 days.
Bouchard, C., A. Tremblay, J.P. Despres, A.Nadeau, P. Lupien, G. Theriault, J. Dussault, S. Moorjani, S. Pinault, and G. Fournier. The response to long-term overfeeding in identical twins. New England Journal of Medicine 332:1477-1482, 1990.
Bouchard and colleagues found not only a similar weight between pairs of twins, but similar distribution of fat gain.
Thus, there is a genetic component to weight or fat gain which can be modified by the environment. Combining the genetic work in overweight and obesity, the contribution is estimated to be:
Set-Point - Theory is simple. In this theory, the body desires to have a specific amount of body fat. No matter what you eat or how hard you exercise, the body will always return to its own target percentage of fat. This theory is supported by rat studies where fat pads are cut out. The fat pad of the rat returns to the size it was before being cut out.
Caloric Balance - Caloric Balance Theory is also simple. If you eat more calories than you expend, you gain fat. If you expend more calories than you eat, you lose fat. With this theory, everyone will gain fat if they eat more calories than they expend.
In the balance of caloric intake and energy expenditure, the factors affecting caloric intake include
whereas the factors affecting energy expenditure include:
Physical activity metabolic rate
Basal metabolic rate
Essential body functions
Lean body mass
Resting metabolic rate
High Fat Nutrient Intake- In this theory, both the quality of the nutrient intake as well as the way food is consumed contribute to overweight and obesity.
Osci and colleagues randomized rats into four groups. The control group at regular nutritionally balanced rat chow. The HI-FAT group at high-fat rat chow; the HI-SUGAR group at high-sugar rat chow; and the fourth group at high fat & sugar chow.
Although the control and HI FAT/SUGAR group ate more calories than the HI-FAT or HI-SUGAR group
the control group exhibited the lowest percent fat.
All three of the HI fat/sugar groups exhibited a high percent body fat.
Thus, the nutrient quality of the food appears to have an influence on weight or fat gain.
Similar patterns can be found in humans. That is, both obese men and women (yellow bars) eat a higher percent of fat (FAT) than lean men and women (red bars).
The opposite is found for carbohydrate intake. Both lean men and women eat a higher percent of carbohydrates (CHO) than lean men and women.
Miller W.C., AK Lindeman, JP Wallace, & M Niederpruem. Diet composition, energy intake, and exercise in relation to body fat in men and women. American Journal of Clinical Nitration 52:426-430, 1990.
Eating patterns may also contribute to overweight and obesity.
In a weight cycling study, Brownell and colleagues exposed rats to a period of overeating followed by a period of dieting, followed by another period of overeating and another period of dieting. They measured how many days it took to gain or lose 130 grams
This figure shows it took almost 50 days to gain the 130 grams during the first weight gain cycle.
The rats then lost weight before overeating again.
For the second weight gain cycle it only took about 10 days.
This figure shows it took about 20 days to lose the 130 grams gained from overeating.
The rats overate again.
For the second weight loss cycle, it took over 40 days to lose the 130 grams.
Twice as Long to Lose Weight
Third the time to Regain the Weight
Redistribution to Upper Body Fat Deposits
Once again, these findings are not isolated to rats. Humans who join weight loss programs exhibit shorter times to regain weight and longer times to lose weight. Humans also weigh more on consecutive cycles.
Rodin, J. N Radke-Sharpe, M. Rebffe-Scrive, and MRC Greenwood. Weight cycling and fat distribution. International Journal of Obesity 14:303-310, 1990.
Rodin and colleagues found an increased incidence of abdominal obesity in women who participated in more weight cycling.
Garrow and colleagues reported decreases in resting metabolic rate with successive caloric restriction activities. In addition, for each event, resting metabolism took longer to return to baseline.
Biochemical Imbalance - There are several biochemical changes that accompany overweight and obesity. The question truly is, which comes first, the excess fat or the changes in endocrine function. Experimental obesity is a condition when a subjects overeats to become obese; whereas spontaneous obesity is more naturally occurring obesity. The characteristics of spontaneous vs. experimental obesity are summarized below:
Free Fatty Acids
no change or increase
All within normal limits
no change or decrease
no change or decrease
no change or decrease
no change or decrease
no change or increase
no change or increase
no change or increase
no change or increase
response to Glucose
response to Arginine
Appetite late in day
Calories required to maintain obesity
It is more difficult to find evidence comparing adipocyte endocrine function between spontaneous vs. experimental obesity. Animal models should offer good information, however, most spontaneous obesity animal models have been genetically engineered; and may not provide adequate information.
Overweight and obese individuals are at increased risk for many diseases and health conditions, including the following:
Osteoarthritis (a degeneration of cartilage and its underlying bone within a joint)
Type 2 diabetes
Coronary heart disease
Congestive Heart Failure
Sleep apnea and respiratory problems
In addition, the severity of these diseases is also greater in overweight and obesity.
The American Heart Association has now elevated overweight and obesity to risk factor status for atherosclerotic cardiovascular disease.
BMI exhibits a "J" shaped curve with mortality ratio. That is, very low BMI is associated with an increased risk of mortality. However, high BMI is strongly associated with significantly increasing mortality.
In addition, the prevalence of diabetes increases with increasing upper body fat distribution.
Higher body fat content significantly increases this risk.
The same is true for hypertension and other diseases.
In all, the life expectancy of the younger generations is anticipated to be shorter for the first time in recording life expectancy.
Fat Contents of Organs
Along with excess body fat is intraorgan fat deposits. The lipid content of every organ increases in overweight and obesity. However, the liver, heart, and the muscle cells may be the most altered by excess fat.
Nonalcoholic Fatty Liver Disease (NAFLD) is the most common cause of liver abnormalities and clinical follow-up.
Approximately 25-33% of the US population is considered to have NAFLD.
Lipid accumulation in the cardiac tissue are associated with conduction defects as lipid can accumulate in the SA node, AV node, and right bundle branch. Accumulating lipid deposits can also form irregular aggregates or bands of adipose tissue that separate myocardial cells. These bands interfere with contraction. Cardiac hypertrophy can result from excess fat deposition and/or increased cardiac work associated with ambulating a heavier body weight.
Excess intramuscular fat deposits are associated with increased lipid metabolism within the muscle.
Stress of Excess Body Fat
Adipose tissue is not dead weight. Adipose tissue is active dynamic tissue. Blood flow to adipose tissue at rest is 2-3 mL/min per 100 grams of adipose tissue; increasing more than ten times during periods of higher metabolic activity. Adipose blood flow increases following a meal.
Excess body weight requires a higher metabolic demand, not only for the adipose tissue, but for the body as a whole. Hemodynamic adjustments to the increased metabolic demands include:
Total Blood volume
Left Ventricular Hypertrophy
Systolic Blood Pressure
Peripheral Vascular Resistance
The relative energy expenditure for various weight dependent activities (wt bearing) activities remains the same (mL/min kg). That is, if walking 3 miles per hour takes 3 METs or 10.5 ml/min kg, it will remain similar for normal weight and overweight individuals. The absolute VO2 (mL/min) to achieve the 3 METs, however, will be higher for the overweight individual; because the the body weight will be higher. To produce 3 METs a 50 kg person would have to provide 525 mL of oxygen/min whereas a 100 kg person would have to provide 1050 mL of oxygen/min.
Weight independent (non weight bearing) work is different. Cycling at 50 Watts requires a oxygen absolute requirement (mL/min), but is modified by body weight. The 50 kg individual requires 715 mL/min to perform 50 Watts whereas the 100 kg individual requires 980 mL/min. However, because of the body weight, the energy expenditure turns out to be 14.3 ml/min kg (4.1 METs) for the 50 kg person and 8.8 ml/min kg (2.5 METs) for the 100 kg person. The non weight bearing activity requires similar absolute (not relative) VO2 the larger person will be performing at a lower VO2 (ml/min kg) relative to body weight because of their excess body weight.
To complicate further, remember VO2 max will be considerably lower in the overweight or obese individual, which makes the standard submaximal work, relative to their max, quite high. Let's say the VO2 max for the 50 kg person is 50.0 ml/min kg (14 METs) and the VO2 max for the 100 kg person is 25.0 ml/min kg (7 METs). The 3 MET requirement for the walking (above) will be 20% for the 50 kg person, but 42% for the 100 kg person. For the cycling, the 50 Watts will be 30% for the 50 kg person, but 36% for the 100 kg person.
Another disadvantage of exercise for overweight adults in an increased oxidative stress during the exercise.
Overweight and obese exhibit higher oxidative stress at rest and following maximal (pictured here) and submaximal exercise.
Vincent MSSE 2005
Other systems of the body are stressed as a result of overweight and obesity.
These activities contribute to the primary diseases associated with overweight and obesity.
Through increased oxidative stress and increased insulin resistance.
Although leptin increases in overweight and obesity, it appears to decrease function. For, example, the hypothalamus becomes resistance to leptin. Thus, the signal for satiety is not recognized; neither are the signals for other endocrine functions which affect the
Hypothalamic-pituitary- gonadal axis
The leptin resistance may be found more in the central nervous system than in the peripheral organs (pancreas, liver & muscle).
Leptin concentrations in obesity appear to be related to the fat mass.
Adiponectin decreases in overweight and obesity. An increase in inflammatory cytokines as well as an increase in insulin resistance may be the initiating factors to decrease adiponectin. The decrease on adiponectin decreases vascular nitric oxide production which decreases endothelial antiatherogenic function.
TNF-alpha is primarily secreted from the macrophage in adipose tissue. TNF-alpha activity increases dramatically in overweight and obesity. TNF-alpha action is to increase insulin resistance leading to metabolic syndrome, diabetes, and atherosclerosis associated with overweight.
IL-6 is another cytokine secreted from the macrophage in adipose tissue and is elevated in overweight and obesity. Its action is to increase insulin resistance; contributing to metabolic syndrome, diabetes, and atherosclerosis.
Substances from the renin-angiotensin system (RAS) are increased in overweight and obesity. Angiotensin II is the most active form and is a potent vasoconstrictor in the vasculature. Hypertension is the primary outcome, however, inflammation and endothelial proliferation are also associated with RAS substances in overweight and obesity. The inflammation and hypertension increase the risk for atherosclerosis.
The increase in resistin found in overweight and obesity increases insulin resistance, leading to metabolic syndrome, diabetes and atherosclerosis.
PAI-1 is elevated in overweight and obesity. The primary function of PAI-1 is to inhibit the fibrinolyis; thus, a decrease in fibrinolysis leads to a hypercoagulable state. In this state, there is an increase in platelet aggregation and fibrinous products in atherosclerotic plaque development.
The pathophysiology of obesity, as it relates to the etiology of atherosclerosis, metabolic syndrome and diabetes is summarized below.
PHYSICAL ACTIVITY AND THE PREVENTION OF WEIGHT GAIN
From an epidemiological perspective, physical activity has greater effectiveness in preventing weight gain than in treating overweight or obesity Cross sectional studies appear stronger than longitudinal studies.
The epidemiological studies are limited by the low incidence of a population that engages in high-intensity exercise. There is a lack of information through transition times in growth and development; i.e. childhood to adolescents or adolescents to adulthood.
The best work in the experimental trials for the prevention of overweight and obesity has been found in animal studies of Osci and colleagues.
One of Osci's early experiments divided rats into three groups. One group was a sedentary (Sed-Free) free eating group that was allowed to eat as much food as desired. The exercise group (Exercise) was also allowed to eat as much as they wanted. However, the third group was sedentary, but the food was restricted so that they would end-up weighing the same as the exercise group (Sed-Pair).
As illustrated to the right, the sedentary free-eaters and exercising rats at the same amount, but the sedentary pair-weighted ate less.
As illustrated in the left panel of the graph on the left, the sedentary free-eating rats (green) weighed more than the others, and the sedentary pair-weighted weighed (blue) weighed the same as the exercising rats (yellow).
The panel to the right shows that the exercise group (yellow) exhibited less body fat that the other two sedentary groups, even when the sedentary pair-weighted group (blue) ate fewer calories.
Similarly, the exercise group (yellow) had fewer fat cells and smaller fat cell size than either of the two sedentary groups (green & blue); even the sedentary group that had restricted calories (blue).
Thus, exercise can result in lower percent body fat even in the presence of high-fat calorie consumption.
The most effective aspects of exercise and physical activity is the reduction of body fat. In a 1983 review, Wilmore reported average lean and fat changes with physical activity in the table to the right. Weights are reported in kilograms.
Wilmore J.H. Appetite and body compostion consequent to physical activity. Research Quarterly for Exercise and Sport 54:415-425, 1983.
In a meta-analysis of 493 studies from 1969-1994, Miller and colleagues found greater weight loss with diet and diet + exercise, but less loss of lean weight with exercise in middle-aged moderately overweight adults.
It is important to note the energy expenditure of these studies was not constant throughout these papers.
On the other hand, Franklin and colleagues found no change in lean mass with exercise in overweight women.
Overweight adults may not increase lean with exercise because they have an increased lean associated with being overweight.
Franklin, B., et al. Research Quarterly 1976
Thus, not all populations will increase lean mass with exercise. Those populations with low lean mass will increase lean mass with exercise.
Maintenance of lean mass during caloric restriction is important for maintaining basal metabolism. Lean mass is a major contributor to basal metabolic rate. A loss in lean body mass decreases basal metabolic rate. The reduction in basal metabolic rate, reduces the caloric need to maintain weight.
The primary exercise for fat loss has been cardiorespiratory. Resistance exercise may be essential in maintaining or building lean weight, and thus, increasing caloric needs. However, resistance exercise, by itself, has exhibited little effect on fat loss. Resistance exercise combined with cardiorespiratory exercise may be the most effective approach to lose body fat while preserving or increasing fat free mass.
Other considerations in the type of exercise for fat loss is the accumulation of physical activity. More recently, the accumulation of physical activity has been recommended. However, the accumulation of physical activity for fat loss has limited studies. Jakicic and colleagues published one study that followed 115 women who were divided into three groups for 18 months.
Long Bout Group - exercised for 40 min in a single session, 5 days a week. (red)
Short Bout Group - exercised four 10 min sessions a day, 5 days a week. (blue)
Short Bout with Equipment - exercised the same as the short bout group, but was given a treadmill at home. (black)
Jakicic, J.M., C. Winters, W. Lang, RR Wing, Effects of intermittent exercise and use of home equipment on adherence, weight loss, and fitness in overweight women: A randomized trial. JAMA 282:1554-1560, 1999
The weight loss was similar at 6 months. The short bout group (blue) lost the least weight whereas the short bout with equipment (black) lost the most and adhered the best.
Thus, accumulating physical activity appears just as effective as a single long workout.
An advantage to accumulating physical activity throughout the day may be in an increased EPOC following each activity bout.
On the same lines as the accumulation of physical activity is whether lifestyle activity is effective in fat loss. Dunn and colleagues provided structured exercise or lifestyle activity to 116 sedentary men and 119 sedentary women for six months. Subjects in the structured exercise joined a fitness facility and exercised 20 - 60 min between 50-85% of VO2max, 5 days a week; whereas the lifestyle group was told to accumulate 30 min of moderate intensity activity on most if not all days of the week. Both groups were instructed in behavior change.
Neither group exhibited a significant weight loss. However, the lifestyle physical activity group had a greater reduction in percent body fat.
For the morbidly obese population, the effectiveness of exercise is limited. In a review of exercise effectiveness for morbidly obese, Hill reported no weight loss in 75% of the studies, a trend in 20% and a weight loss 5%. Thus, exercise does not appear to be effective in the morbid obese.
Maintenance of Fat Loss
Maintenance of fat loss is defined different ways
individuals who have lost 10% of their body weight and kept it off for one year
< 5 pound weight variation after weight loss
< 3% change in body weight
Approximately 20% appear to fit this definition (individuals who have lost 10% of their body weight and kept it off for one year). There are too few studies that investigate weight maintenance. The National Weight Control Registry recruits individuals with successful weight loss and surveys them for their success factors. This registry tracks over 5000 people who have successfully lost 30 pounds and kept it off for at least on year.
Registry members have lost an average of 66 lbs and kept it off for 5.5 years. Most report continuing to maintain a low calorie, low fat diet and doing high levels of activity.
Fogelholm and colleagues conducted one of the few studies to randomize sedentary subjects into weight maintenance programs following a weight loss. The weight loss program was a 12 week low to very low calorie restriction with behavioral strategies to lose weight. After the weight loss, the three maintenance groups were
Control - no physical activity
Walk 1 - 2-3 hours/week @ 50-60% of HR reserve
Wako 2 - 4-6 hours/week @ 50-60% of HR reserve
the weight maintenance program was 40 additional weeks.
As illustrated to the right, the control group gained weight, fat mass and waist circumference.
Whereas both walking groups, not only kept the weight off, but lost a little more.
Two years later, all three groups had gained weight. The walking groups had discontinued walking.
Exercise and Body Fat Distribution/Reduction
Individuals with upper body fat distribution tend to
lose fat more fat than individuals with lower body fat distribution
lose more fat from the abdominal deposits
lower waist:hip ratio than individuals with lower body fat distribution
Walden et al, Am J Clin Nutr 47:229-234, 1988
FAT CELL CHARACTERISTICS
Very few studies have focused on fat cell size and number with the reduction of body weight through exercise and physical activity.
Salans observed fat cell size and number in experimental obesity and the subsequent reduction in body fat. Fat cell size increased in experimental obesity, whereas fat cell number did not change. Fat cell number also did not change in body fat reduction.
When it comes to fat cell size, exercise is limited in how much the fat cell size will decrease. Tremblay observed the fat cell size of elite marathoners (red bars), sedentary controls (blue bars) and marathon runners who used to be obese (yellow bars).
The percent body fat for the elite runners was the lowest. The percent body fat for the ex obese runners was higher than the elite runners, but similar to the sedentary controls.
Interestingly, the fat cell size was smallest for the ex obese runners and largest for the sedentary controls. The elite runners probably had a normal fat cell size. The fat cell size of the ex obese runners was probably as small as it could be.
Not all individuals who exercise will be effective in reducing body fat. Bouchard has labeled some as responders and nonresponders based on the total amount of fat weight lost. Bouchard not only found that pairs of twins gain similarly in overeating studies, but that pairs lose similarly when calories are restricted.
Less Weight Cycling
Upper Body Fat Distribution
Highly Motivated & Ready
FITNESS & FATNESS
Target weights for health are not necessarily the ideal weights often used for athletic performance. A 5-10% reduction in body weight may significantly improve health. A sustained target weight should be approximately >10% of initial body weight.
Lee and colleagues divided 21,925 men into lean (<16.7% fat), normal, and obese (>25% fat). These three groups were further subdivided into fit and unfit categories based on treadmill time (range of estimated max METs was 8.7 METs (obese unfit) to 13.4 METs (lean fit). The figure to the right illustrates that fit obese men exhibit a risk similar to the lean fit men. Similar findings were reported for women.
What mechanisms from exercise protect the obese man from disease?
Osci and colleagues (reported earlier) found that exercise can counteract the effects of a high-fat diet.
Energy expenditure can increased not only during the exercise, but in the recovery from exercise. Can energy expenditure be increased at rest?
This graph illustrates that resting metabolic rate (x axis) increases with VO2max.
The primary question regarding this relationship is the lean body mass. Is there a similar relationship between lean body mass and VO2max?
The graph below not only illustrates the increase in energy expenditure (O2 consumption) during the physical activity, but the increase in energy expenditure in recovery. The EPOC, excess post exercise oxygen consumption, depends more on the intensity of exercise than the duration of exercise and has been document to last up to 24 hours after exercise.
There are conflicting reports on what exercise does to appetite or food intake.
According to Neiman and colleagues, food intake decreased during a 15 week exercise program in previously sedentary women, whereas the control group increased food intake.
On the other hand, Woo compared the food intake to the energy expenditure of sedentary, mild and moderately active women. They found that energy intake did not increase significantly as the amount of exercise progressed.
Thus, the information on energy intake for exercise and physical activity for weight loss studies are not clear.
A single session of most types of exercise, including resistance exercise is sufficient to increase insulin sensitivity, in healthy, obese, and type 2 diabetic adults. The only exception to an exercise induced increase in insulin sensitivity is marathon running and intense downhill running. Similarly, exercise training improves insulin sensitivity regardless of age, in healthy, obese and type 2 diabetic adults; even with no change in VO2max. Changes in insulin sensitivity associated with exercise vanish within 3-5 days; and can be regained after a single exercise session.
Eriksson J, Taimela S, Koivisto VA. Exercise and the metabolic syndrome. Diabetologia. 1997;40:125-135.
Dynamic exercise (acute or chronic) causes a significant, moderately large decrease in postprandial lipemia. There appears to be no influence of exercise intensity, duration, or time between exercise and the meal on the attenuation of postprandial lipemia. The sequence of the exercise, before or after the meal, did not affect the decrease in postprandial lipemia. Even the accumulation of intermittent physical activity throughout a single day is as effective in reducing postprandial lipemic load as one session of continuous exercise. The exercise-induced reduction in postprandial lipemia is independent of the metabolic substrate utilized during exercise.
Petitt DS, Cureton KJ. Effects of prior exercise on postprandial lipemia: A quantitative review. Metabolism. 2003;52:418-424.
Katsanos CS, Moffatt RJ. Acute effects of premeal versus postmeal exercise on postprandial hypertriglyceridemia. Clinical Journal of Sports Medicine. 2004;14:33-39
The figure to the right illustrates how much lower the postprandial lipid load is following one bout of exercise. Twelve healthy adults ate a high fat meal. One time without exercise (control; red line) and another time following exercise (blue line). The exercise was a two hour walk on a treadmill at 39% of VO2max.
ADIPOSE ENDOCRINE FUNCTION IN EXERCISE
The literature on adipokines and exercise is limited. Specific questions regarding
Diet was increased consumption of fish and fish products, vegetables and fiber-rich products of complex carbohydrates with reduction of high fat foods and cholesterol
Exercise was supervised endurance, circuit training, fasting walking or jogging, 3/week for 60 min. The intensity was not given.
Significant weight losses were found in all three groups and not the control group. Larger weight losses were found in the diet and diet and exercise groups compared to the exercise only group. Similar findings were reported for percent body fat.
The only findings for adipokines were adiponectin and TNF alpha.
Adiponectin significantly decreased in the control group, yet remained unchanged in the intervention groups; changes were related to fat mass. Whereas, TNF alpha increased in the diet and exercise interventions, yet decreased in the combined diet and exercise group; thus, exhibiting a significant interaction. Minor changes were found in the remaining adipokines.
Leptin has been investigated more extensively than any of the adipokines. The change in leptin may be due to a negative energy balance. Leptin concentrations of obese type 2 diabetic adults appear to respond to exercise better than normal weight adults.
Single session of exercise may or may not affect leptin.
Short-term (<60 min) does not change leptin in men or women
Long-term (>60 min) appears to reduce leptin, however, it may be an effect of diurnal rhythm rather than exercise
It appears as though high intensity-long duration decreases leptin
Resistance exercise can produce a delayed (9 hr post) reduction in leptin
Long-term exercise training (>12 weeks) decreases circulating leptin, independent of the fat mass.
Short-term training (<12 weeks) does not alter leptin in men or women
exception is a reduction in leptin in Type 2 diabetes
Adiponectin has been measured in conditions of acute and long-term exercise in healthy and overweight/obese adults.
Single session of exercise does not affect adiponectin in healthy men and women.
Exercise training does not affect adiponectin in healthy men, despite increases in insulin sensitivity.
Exercise training does not affect adiponectin in type 2 diabetes, despite increases in insulin sensitivity.
Exercise training without weight loss has no affect on adiponectin.
It appears as though weight loss has the biggest effect on adiponectin increases; and that increases in insulin sensitivity are mediated through increases in adiponectin.
Distinguishing the effects of exercise on the TNF alpha production of adipocytes from other cells is difficult.
Single session of exercise had no effect on TNF alpha in diabetic and nondiabetic controls
Prolonged exercise did not change TNF alpha in trained men
Combined water aerobics + resistance exercise training increased TNFalpha in women
Diet + exercise training in glucose intolerant subjects and diabetic subjects decreased TNF alpha
Similar to TNF alpha, IL-6 is produced from several types of cells. The fact that skeletal muscle contraction increases IL-6 is well documented. However, the adipocyte production of IL-6 associated with exercise has not been investigated as extensively.
a single session of exercise increased subcutaneous adipose IL-6 secretion and IL-6 mRNA expression
No effect of exercise on resistin activity in adipocytes in a limited number of studies.
The clinical management of overweight and obesity includes:
GUIDELINES FOR THE TREATMENT OF OVERWEIGHT & OBESITY
The National Heart, Lung, and Blood Institute, in cooperation with the National Institute of Diabetes and Digestive and Kidney Diseases, released the first Federal guidelines on the identification, evaluation, and treatment of overweight and obesity in 1998.
Measure height and weight to calculate Body Mass Index (BMI).
BMI = weight (kg)/height (m2)
BMI should be interpreted as:
MEASURE WAIST CIRCUMFERENCE
Increased Relative Risk to Normal Weight and Waist Circumference
25.0 - 29.9
30.0 - 34.9
35.0 - 39.9
Extreme Obesity III
Comorbidities not only include modern chronic disease but the risk factors for cardiovascular disease as well.
Existence of the following diseases classify a patient with very high absolute risk.
Coronary heart disease
Any atherosclerotic related disease
Type 2 diabetes
A patient is considered high risk of three or more of the following risk factors are positive:
Systolic >140 mm Hg or
Diastolic >90 mm Hg or
Taking antihypertensive agents
130-159 mg/dL with tow or more risk factors
Impaired fast ing glucose
Male first degree relatives >55 years old
Female first degree relatives >65 years old
Men >45 years old
Women > 55 years old or postmenopausal
Clinical judgement can also be considered for the following factors:
Progressive weight gain since adolescence
History of obesity
Binge Eating Disorder
Relevant medical conditions
Overall disease burden
Quality of Life
Factors that may exclude a patient from weight loss:
Unstable mental illness
Unstable medical conditions
The decision to lose weight must be an agreement between the health care provider and the patient. If the patient does not want to lose weight, he/she should be encouraged to maintain current weight, not to gain more weight.
Based on the degree of overweight/obesity and health risk, the following treatment are options:
Increase physical activity
Increase physical activity
Decrease food intake
Increase physical activity
Decrease food intake
Increase physical activity
Decrease food intake
The NIH treatment guide:
Prevention of weight gain with lifestyle therapy is indicated in any patient with a BMI ≥ 25 kg/m2,
even without comorbidities, while weight loss is not necessarily recommended for those with a BMI
of 25–29.9 kg/m2 or a high waist circumference, unless they have two or more comorbidities.
Combined therapy with a low-calorie diet (LCD), increased physical activity, and behavior therapy
provide the most successful intervention for weight loss and weight maintenance.
Consider pharmacotherapy only if a patient has not lost 1 pound per week after 6 months of
combined lifestyle therapy.
The + represents the use of indicated treatment regardless of comorbidities.
IS THE PATIENT READY AND MOTIVATED?
A patient can be motivated to lose weight, but not ready to do so. A valid and reliable method is needed to determine these factors. Clinical questions to help determine readiness:
Has the individual sought weight loss on his or her own initiative?
What events have led the patient to seek weight loss now?
What are the patient's stress level and mood?
Does the individual have an eating disorder, in addition to obesity?
Does the individual understand the requirements of treatment and believe that he or she can fulfill them?
How much weight does the patient expect to lose? What other benefits does he or she anticipate?
Self-efficacy may be the best predictor of success than any other behavioral variable.
The three alternatives are
to lose weight
to maintain weight at a lower weight
Prevent further weight gain
If the patient is ready utilize health care providers:
Health Care Provider
Increase Physical Activity
Join a program
Seek advice of exercise professional
join a clinical program
Low or Very Low Calorie Diet
CHOOSE A DIET
Weight should be lost at a rate of 1-2 pounds per week based on a deficit of 500-1000 kcal/day.
Low Calorie Diet is the recommended diet (above). However, a Very Low Calorie Diet can also be recommended; <800 kcal/day.
Specific diets can also be chosen to target diabetes, hypertension or hyperlipidemia.
Some of the most commonly used FDA approved drugs for pharmacotherapy of obesity are based on lowered fat digestion and absorption in intestine, appetite suppression, and central nervous system stimulant.
MECHANISM OF ACTION
Appetite suppressant- similar to amphetamine acting on the central nervous system
Appetite suppressant - a central acting serotonin-norepinepherine reuptake inhibitor; related to amphetamines
Dexedrine (Dextroamphetamine Saccharate)
CNS Stimulant - an amphetamine analog
Reduction in fat absorption via inhibition of pancreatic lipase activity in intestine
Over the Counter
Amphetamines is a psychostimulant that increases wakefullness and focus and is associated with decreased fatigue and appetite. Amphetamines affect dopamine, serotonin and norepinepherine in the central nervous system.
Antidiabetic medications also counteract some of the endocrine abnormalities found in overweight and obesity, but these meds are not incorporated as typical treatments in obesity.
ADIPOSE ENDOCRINE SUBSTANCES
Reduces hepatic glucose
Increases muscle insulin sensitivity
Improves hepatic & peripheral insulin sensitivity
block Angiotensin Converting Enzyme
A summary of the physical activity and exercise requirements are summarized below. These recommendations given by the American College of Sports Medicine.
>250 min/wk of moderate (3.0-5.9 METs) physical activity
Overweight and obesity affects more than 66% of the adult population and is associated with a variety of chronic diseases. Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies. Guidelines of the National Heart, Lung, and Blood Institute (NHLBI) encourage a 10% reduction in weight, although considerable literature indicates reduction in health risk with 3% to 5% reduction in weight. Physical activity (PA) is recommended as a component of weight management for prevention of weight gain, for weight loss, and for prevention of weight regain after weight loss. In 2001,
the American College of Sports Medicine (ACSM) published a Position Stand that recommended a minimum of 150 min/wk of moderate intensity PA for overweight and obese adults to improve health; however, 200–300 min/wk was recommended for long-term weight loss. More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss. To this end, we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain, for weight loss, and prevention of weight regain. Evidence supports:
Moderate intensity PA between 150 and 250 min/wk to be effective to prevent weight gain.
Moderate-intensity PA between 150 and 250 min/wk will provide only modest weight loss.
Greater amounts of PA (9250 min/wk) have been associated with clinically significant weight loss.
Moderate intensity PA between 150 and 250 min/wk will improve weight loss in studies that use moderate diet restriction but not severe diet restriction.
Cross-sectional and prospective studies indicate that after weight loss, weight maintenance is improved with PA 9250 min/wk.
However, no evidence from well-designed randomized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss. Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk. Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk. There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain.
UTILIZING BEHAVIORAL TECHNIQUES
Behavior change may be the key to success in weight management. People need help making behavioral change when there is no threatening medical catastrophe imminent. Behavioral techniques are discussed below.
The Treatment Algorithm:
BEHAVIORAL TECHNIQUES FOR WEIGHT LOSS
Behavioral techniques for weight loss revolve around diet and exercise interventions. The use of behavioral techniques are not new. In 1963 Ferster and colleagues proposed operant conditioning to modify eating behavior. Among their recommendations were having overwieght patients recite the adverse effects of being fat and look at unattractive pictures of themselves in bathing suits.
Ferster, C. B., Numberger, J. I., & Levitt, E. E. (1%2). The control of eating. Journal
of Mathetics, 1, 87-109.
More scientifically controlled behavioral studies began in the early 1979s; in 5 years 45 studies were published on behavioral approaches to weight loss and maintainence. However, these offered strategies for behavior change rather than appliying a behavioral theory. The behavioral techniques included:
Stimulus control techniques (two lessons)
Slowing the rate of eating
Generating social support
Exercise (two lessons)
Individual problem solving
This first 1978 review concluded that behavioral approaches produce consistent, but modest weigth loss (11.0 pounds; range +7 to - 47 lbs) which could be maintained over one year.
In 1991 Garner and colleagues addressed the failure of weight loss programs. Their diagram to the left, taken out of a 1981 review has not changed. The major obsticle for all researchers is to achieve perminant weight loss in overweight and obese patients.
Among thier conclusion/summary was the comment of "It is difficult to find any scientific justification for the continued use of dietary
treatments of obesity." They also implied that it may be more unhealthy to continually weight cycle. The physiological and genetic influences are believed to be stronger than the desire to lose weight, according to Garner and colleagues.
Even though behavioral intervention may help weight loss or adoption of exercise behaviors, if the patient is not ready to make the changes, behavioral techniques may not be successful.