the obesity: causes & treatment

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems. Body mass index (BMI), a measurement which compares weight and height, defines people as overweight (pre-obese) when their BMI is between 25 kg/m2 and 30 kg/m2, and obese when it is greater than 30 kg/m2.
Obesity increases the likelihood of various diseases, particularly heart disease, type 2 diabetes, breathing difficulties during sleep, certain types of cancer, and osteoarthritis. Obesity is most commonly caused by a combination of excessive dietary calories, lack of physical activity, and genetic susceptibility, although a few cases are caused primarily by genes, endocrine disorders, medications or psychiatric illness. Evidence to support the view that some obese people eat little yet gain weight due to a slow metabolism is limited; on average obese people have a greater energy expenditure than their thin counterparts due to the energy required to maintain an increased body mass.

Causes:

At an individual level, a combination of excessive caloric intake and a lack of physical activity is thought to explain most cases of obesity. A limited number of cases are due primarily to genetics, medical reasons, or psychiatric illness. In contrast, increasing rates of obesity at a societal level are felt to be due to an easily accessible and palatable diet, increased reliance on cars, and mechanized manufacturing.
A 2006 review identified ten other possible contributors to the recent increase of obesity: (1) insufficient sleep, (2) endocrine disruptors (environmental pollutants that interfere with lipid metabolism), (3) decreased variability in ambient temperature, (4) decreased rates of smoking, because smoking suppresses appetite, (5) increased use of medications that can cause weight gain (e.g., atypical antipsychotics), (6) proportional increases in ethnic and age groups that tend to be heavier, (7) pregnancy at a later age (which may cause susceptibility to obesity in children), (8) epigenetic risk factors passed on generationally, (9) natural selection for higher BMI, and (10) assortative mating leading to increased concentration of obesity risk factors (this would not necessarily increase the number of obese people, but would increase the average population weight). While there is substantial evidence supporting the influence of these mechanisms on the increased prevalence of obesity, the evidence is still inconclusive, and the authors state that these are probably less influential than the ones discussed in the previous paragraph.

Diet-
The per capita dietary energy supply varies markedly between different regions

and countries. It has also changed significantly over time. From the early 1970s to the late 1990s the average calories available per person per day (the amount of food bought) has increased in all parts of the world except Eastern Europe. The United States had the highest availability with 3,654 calories per person in 1996. This increased further in 2003 to 3,754. During the late 1990s Europeans had 3,394 calories per person, in the developing areas of Asia there were 2,648 calories per person, and in sub-Saharan Africa people had 2,176 calories per person. Total calorie consumption has been found to be related to obesity.
The widespread availability of nutritional guidelines has done little to address the problems of overeating and poor dietary choice. From 1971 to 2000, obesity rates in the United States increased from 14.5% to 30.9%. During the same period, an increase occurred in the average amount of calories consumed. For women, the average increase was 335 calories per day (1,542 calories in 1971 and 1,877 calories in 2004), while for men the average increase was 168 calories per day (2,450 calories in 1971 and 2,618 calories in 2004). Most of these extra calories came from an increase in carbohydrate consumption rather than fat consumption. The primary source of these extra carbohydrates are sweetened beverages, which now account for almost 25 percent of daily calories in young adults in America. Consumption of sweetened drinks is believed to be contributing to the rising rates of obesity.
As societies become increasingly reliant on energy-dense, big-portion, fast-food meals, the association between fast-food consumption and obesity becomes more concerning. In the United States consumption of fast-food meals tripled and calorie intake from these meals quadrupled between 1977 and 1995.
Agricultural policy and techniques in the United States and Europe have led to lower food prices. In the United States, subsidization of corn, soy, wheat, and rice through the U.S. farm bill has made the main sources of processed food cheap compared to fruits and vegetables.
Obese people consistently under-report their food consumption as compared to people of normal weight. This is supported both by test of people carried out in a calorimeter rooms and by direct observation.

-Sedentary lifestyle
A sedentary lifestyle plays a significant role in obesity. Worldwide there has

been a large shift towards less physically demanding work, and currently at least 60% of the world's population gets insufficient exercise. This is primarily due to increasing use of mechanized transportation and a greater prevalence of labor-saving technology in the home. In children there appears to be declines in levels of physical activity due to less walking and physical education. World trends in active leisure time physical activity are less clear. The World Health Organization indicates that people worldwide are taking up less active recreational pursuits, while a study from Finland found an increase and a study from the United States found leisure-time physical activity has not changed significantly.
In both children and adults there is an association between television viewing time and the risk of obesity. A 2008 meta-analysis found that 63 of 73 studies (86%) showed an increased rate of childhood obesity with increased media exposure, with rates increasing proportionally to time spent watching television.

-Genetics
Like many other medical conditions, obesity is the result of an interplay

between genetic and environmental factors. Polymorphisms in various genes controlling appetite and metabolism predispose to obesity when sufficient calories are present. As of 2006 more than 41 of these sites have been linked to the development of obesity when a favorable environment is present. The percentage of obesity that can be attributed to genetics varies, depending on the population examined, from 6% to 85%.
Obesity is a major feature in several syndromes, such as Prader-Willi syndrome, Bardet-Biedl syndrome, Cohen syndrome, and MOMO syndrome. (The term "non-syndromic obesity" is sometimes used to exclude these conditions.) In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single point DNA mutation.
Studies that have focused upon inheritance patterns rather than upon specific genes have found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.
The thrifty gene hypothesis postulates that certain ethnic groups may be more prone to obesity in an equivalent environment. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would be more likely survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This is the presumed reason that Pima Indians, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.

-Infectious agents
The study of the effect of infectious agents on metabolism is still in its early stages. Gut flora has been shown to differ between lean and obese humans. There is an indication that gut flora in obese and lean individuals can affect the metabolic potential. This apparent alteration of the metabolic potential is believed to confer a greater capacity to harvest energy contributing to obesity. Whether these differences are the direct cause or the result of obesity has yet to be determined unequivocally.
An association between viruses and obesity has been found in humans and several different animal species. The amount that these associations may have contributed to the rising rate of obesity is yet to be determined.

Diseases caused by obesity:

 

1. Cardiovascular
• Congestive Heart Failure
a condition in which the heart can’t pump enough blood to the body’s other organs.
• Enlarged Heart
an increase in the size of the heart that may be caused by a thickening of the heart muscle because of increased workload.
• Cor Pulmonale
Also known as right heart failure. Cor pulmonale is a change in structure and function of the right ventricle of the heart as a result of a respiratory disorder.
• Varicose Veins
Twisted, enlarged veins that mostly affects the lower body as a result of pressuring the veins.
• Pulmonary Embolism
• Blockage of the pulmonary artery (or one of its branches) by a blood clot, fat, air, amniotic fluid, injected talc or clumped tumor cells that results in difficulty breathing, pain during breathing, and more rarely circulatory instability and may result in death.

2. Endocrine
• Polycystic Ovarian Syndrome (PCOS)
Cysts (fluid-filled sacs) in the ovaries that result in high levels of androgens (male hormones) and missed or irregular periods.
• Menstrual Disorder
is a physical or emotional problem that interferes with the normal menstrual cycle, causing pain, unusually heavy or light bleeding, delayed menarche, or missed periods.

• Infertility
inability for a man or woman to contribute to conception

3. Gastrointestinal
• Gastroesophageal Reflux Disease (GERD)
happens when the LES ,a ring of muscle at the bottom of the esophagus that acts like a valve between the esophagus and stomach, opens spontaneously for varying periods of time which causes stomach contents along with digestive juices to rise up into the esophagus (the tube that carries food from mouth to stomach).
• Fatty Liver Disease
an accumulation of fat within the liver that may cause liver-damaging inflammation and, sometimes, the formation of fibrous tissue. In some cases, this can progress either to cirrhosis, which can produce progressive, irreversible liver scarring, or to liver cancer.
• Cholelithiasis (gallstones)
Gallstones form when bile, liquid that help the body digest fats, that is stored in the gallbladder hardens into pieces of stone-like material. Happens when bile contains too much cholesterol.
• Hernia
occurs when the contents of a body cavity bulge out of the area where they are normally contained. These contents, usually portions of intestine or abdominal fatty tissue, are often enclosed in the thin membrane that naturally lines the inside of the cavity.
• Colorectal Cancer
also known as colon cancer, is cancerous growths in the colon, rectum and appendix. It is the third most common form of cancer and the second leading cause of death among cancers in the Western world.

4. Renal and Genitourinary
• Erectile Dysfunction
also known as impotence is the inability to get or keep an erection firm enough for sexual intercourse.
• Urinary Incontinence
is the loss of bladder control that results in mild leaking to uncontrollable wetting
• Chronic Renal Failure
is a gradual and progressive loss of the ability of the kidneys to excrete wastes, concentrate urine, and conserve electrolytes.
• Hypogonadism
happens when the sex glands produce little or no hormones. In men, these glands (gonads) are the testes; in women, they are the ovaries.
• Breast Cancer
is the most common cancer among women
• Uterine Cancer
Symptoms include
o Unusual vaginal bleeding or discharge
o Trouble urinating
o Pelvic pain
o Pain during intercourse
• Stillbirth
occurs when a fetus which has died in the womb or during labour or delivery exits its mother’s body.

5. Integument (skin and appendages)
• Stretch Marks
are fine lines that appear on the skin that appears when a person grows or gains weight really fast.
• Acanthosis Nigricans
velvety, light-brown-to-black, markings usually on the neck, under the arms or in the groin.
• Lymphedema
is a condition of localized fluid retention caused by a compromised lymphatic system. Danger lies in the constant risk of developing an uncontrolled infection in the affected limb.
• Cellulitis
Cellulitis appears as a swollen, red area of skin that feels hot and tender, and it may spread rapidly.
• Carbuncles
a skin infection that often involves a group of hair follicles. The infected material forms a lump, called mass, which occurs deep in the skin.
• Intertrigo
bacterial, fungal, or viral infection that has developed at the site of broken skin due to inflammation.

6. Musculoskeletal
• Hyperuricemia
High level of uric acid in the blood that will most likely lead to gout.
• Immobility
is the disease that requires complete bed rest or extremely limits your activity.
• Osteoarthritis
is a joint disease caused by the breakdown and loss of the cartilage of one or more joints.
• Low Back Pain
is the result of trauma to the lower back or a disorder such as arthritis.

7. Neurologic
• Stroke
is a rapidly developing loss of brain function due to an interruption in the blood supply to all or part of the brain.
• Meralgia Paresthetica
is a disorder characterized by tingling, numbness, and burning pain in the outer side of the thigh.
• Headache
is a condition of pain in the head.
• Carpal Tunnel Syndrome
occurs when the median nerve, which runs from the forearm into the hand, becomes pressed or squeezed at the wrist. The median nerve controls sensations to the palm side of the thumb and fingers, as well as impulses to some small muscles in the hand that allow the fingers and thumb to move.
• Dementia
is the progressive decline in cognitive function due to damage or disease in the brain beyond what might be expected from normal aging.

8. Respiratory
• Dyspnea
also known as short of breath (SOB) is perceived difficulty breathing or pain on breathing.
• Obstructive Sleep Apnea
is a sleep disorder characterized by pauses in breathing during sleep with each breathless period lasting long enough so one or more breaths are missed, and occur repeatedly throughout sleep.
• Hypoventilation Syndrome
occurs when a very obese person does not breathe enough oxygen while sleeping. Comes from a defect in the brain’s control over breathing and excessive weight (due to obesity) against the chest wall, which makes it hard for a person to take a deep breath. As a result, the blood has too much carbon dioxide and not enough oxygen.
• Pickwickian Syndrome
is the combination of severe obesity, suffering from obstructive sleep apnea causing hypoxia and hypercapnia resulting in marked daytime somnolence and chronic respiratory acidosis.
• Asthma
is a chronic disease that affects your airways, which are the tubes that carry air in and out of your lungs.

9. Psychological
• Depression
is a state of intense sadness, melancholia or despair that has advanced to the point of being disruptive to an individual’s social functioning and/or activities of daily living.

Psychological Effects of Obesity:

In the United States alone, the psychological effect of obesity is a serious issue

that should be dealt with. More children, teens and adults are becoming overweight at a much earlier age than in the past 5 decades. Obesity brings with it the numerous other diseases from bone & joint problems to respiratory and Type 2 diabetes. It has been noted that once a person begins to lose weight these health risks and problems significantly decrease and in some cases disappear completely.

One of the obvious side effects of obesity that is rarely mentioned is the psychological effects of obesity and what comes with it. Recent studies have established that even although a person manages to lose the weight in their adults years, the psychological damage from being an obese child can still be, in most cases present. Children who are obese tend to have serious self esteem issues and less self confidence in social situations than their generally healthy peers. In many cases obese children will try to avoid gym classes because of shame or embarrassment of their appearance.

To add to the pain obese children endure concerning their poor body images is the teasing they tend to have to endure at school and in many other social settings with their peers. In many cases obese children will go as far as skipping school or even drop out in order to avoid the teasing they get head on.

In recent years it was believed that overweight or obese people were compulsive eaters, depressed, under stress, anxious or trying to over compensate for deficiencies they felt they had in their lives. Today however, almost everyone seems to be getting heavier and obesity has become a national issue. Both obesity experts and the public at large are dismissing the idea that weight gain is nothing but a personal or emotional problem.
With the obvious abundance of overweight people there is plenty of room for exceptions. Many researchers suggests that people who are depressed are more likely to develop the metabolic syndrome that will often accompany excess weight. People may console themselves with "comfort food", which is usually high in fat, sugar, and calories because they are anxious, lonely, angry, or suffering from low self-esteem.

There is also a type of depression that has symptoms that may include lethargy or overeating. As with most mind & body interactions obesity can generally lead to ill health which in turn is linked to case of depression and/or anxiety.

One of the best ways to conquer obesity to is to first acknowledge the situation and then to get help from a professional. One shouldn't hesitate getting help regarding their situation.

Treatments and drugs:

The goal of obesity treatment is to reach and stay at a healthy weight. You may need to work with a team of health professionals, including a nutritionist, dietitian, therapist or an obesity specialist, to help you understand and make changes in your eating and activity habits.
You can start feeling better and seeing improvements in your health by just introducing better eating and activity habits. The initial goal is a modest weight loss — 5 to 10 percent of your total weight. That means that if you weigh 200 pounds (91 kg) and are obese by BMI standards, you would need to lose only about 10 to 20 pounds (4.5 to 9.1 kg) to start seeing benefits.
All weight-loss programs require changes in your eating habits and increased physical activity. The treatment methods that are right for you depend on your level of obesity, your overall health and your willingness to participate in your weight-loss plan. Other treatment tools include:

Dietary changes
Reducing calories and eating healthier are vital to overcoming obesity. Although you may lose weight quickly at first, slow and steady weight loss of 1 or 2 pounds (1/2 to 1 kilogram) a week over the long term is considered the safest way to lose weight and the best way to keep it off permanently. Avoid drastic and unrealistic diet changes, such as crash diets, because they're unlikely to help you keep excess weight off for the long term.

Exercise and activity
Increased physical activity or exercise also is an essential part of obesity treatment. Most people who are able to maintain their weight loss for more than a year get regular exercise, even simply walking.

Behavior changes
A behavior modification program can help you make lifestyle changes, lose weight and keep it off. Steps to take include examining your current habits to find out what factors, stresses or situations may have contributed to your obesity.

Prescription weight-loss medication
Losing weight requires a healthy diet and regular exercise. But in certain situations, prescription weight-loss medication may help. Keep in mind, though, that weight-loss medication is meant to be used along with diet, exercise and behavior changes, not instead of them. If you don't make these other changes in your life, medication is unlikely to work.

Prescription weight-loss medications your doctor may prescribe include:

• Orlistat (Xenical). Orlistat is a weight-loss medication that has been approved by the Food and Drug Administration (FDA) for long-term use in adults and children 12 and older. This medication blocks the digestion and absorption of fat in your stomach and intestines. Unabsorbed fat is eliminated in the stool. Average weight loss with orlistat is about 5 to 7 pounds (2.3 to 3.2 kilograms) more than you can get from diet and exercise after one or two years of taking the medication.

Side effects associated with orlistat include oily and frequent bowel movements, bowel urgency, and gas. These side effects can be minimized as you reduce fat in your diet. Because orlistat blocks absorption of some nutrients, take a multivitamin while taking orlistat to prevent nutritional deficiencies.

The FDA has also approved a reduced-strength version of orlistat (Alli) that's sold over-the-counter, without a prescription. Alli is not approved for children. This medication works the same as prescription-strength orlistat and is meant only to supplement — not replace — a healthy diet and regular exercise.

• Lorcaserin (Belviq). Lorcaserin is a long-term weight-loss drug approved by the FDA for adults in 2012. It works by affecting chemicals in your brain that help decrease your appetite and make you feel full, so you eat less. Your doctor will carefully monitor your weight loss while taking lorcaserin. If you don't lose about 5 percent of your total body weight within 12 weeks of taking lorcaserin, it's unlikely the drug will work for you and the medication should be stopped.

Side effects of lorcaserin include headaches, dizziness, fatigue, nausea, dry mouth and constipation. Rare but serious side effects include a chemical imbalance (serotonin syndrome), suicidal thoughts, psychiatric problems, and problems with memory or comprehension. Pregnant women shouldn't take lorcaserin.

• Phentermine-topiramate (Qsymia). This weight-loss medication is a combination drug approved by the FDA for long-term use in adults. Qsymia combines phentermine, a weight-loss drug prescribed for short-term use, with topiramate, a medication that's used to control seizures. Your doctor will monitor your weight loss while taking the drug. If you don't lose at least 3 percent of your body weight within 12 weeks of starting treatment, your doctor may suggest either stopping use of Qsymia or increasing your dose, depending on your condition.

Side effects include increased heart rate, tingling of hands and feet, insomnia, dizziness, dry mouth and constipation. Serious but rare side effects include suicidal thoughts, problems with memory or comprehension, sleep disorders and changes to your vision. Pregnant women shouldn't take Qsymia. Qsymia increases the risk of birth defects.

• Phentermine (Adipex-P, Suprenza). Phentermine is a weight-loss medication for short-term use (three months) in adults. Using weight-loss medications short-term doesn't usually lead to long-term weight loss. While some health care providers prescribe phentermine for long-term use, few studies have evaluated its safety and weight-loss results long term.

You need close medical monitoring while taking a prescription weight-loss medication. Also, keep in mind that a weight-loss medication may not work for everyone. If the medication does work, its effects tend to level off after six months of use like any other method of weight loss. You may need to take a weight-loss medication indefinitely. When you stop taking a weight-loss medication, you're likely to regain much or all of the weight you lost.

Weight-loss surgery
In some cases, weight-loss surgery, also called bariatric surgery, is an option.

Weight-loss surgery offers the best chance of losing the most weight, but it can pose serious risks. Weight-loss surgery limits the amount of food you're able to comfortably eat or decreases the absorption of food and calories, or both.

Weight-loss surgery for obesity may be considered if:

• You have extreme obesity, with a body mass index (BMI) of 40 or higher
• Your BMI is 35 to 39.9, and you also have a serious weight-related health problem, such as diabetes or high blood pressure
• You're committed to making the lifestyle changes that are necessary for surgery to work

Weight-loss surgery can often help you lose as much as 50 percent or more of your excess body weight. But weight-loss surgery isn't a miracle obesity cure. It doesn't guarantee that you'll lose all of your excess weight or that you'll keep it off long term. Weight-loss success after surgery depends on your commitment to making lifelong changes in your eating and exercise habits.

Common weight-loss surgeries include:

Gastric bypass surgery

Laparoscopic adjustable gastric banding (LAGB)

Gastric sleeve

Biliopancreatic diversion with duodenal switch

Preventing weight regain after obesity treatment
Unfortunately, it's common to regain weight no matter what obesity treatment

methods you try. But that doesn't mean your weight-loss efforts are futile.
One of the best ways to prevent regaining the weight you've lost is getting regular physical activity. Keep track of your physical activity if it helps you stay motivated and on course. As you lose weight and gain better health, talk to your doctor about what additional activities you might be able to do and, if appropriate, how to give your activity and exercise a boost.
You may always have to remain vigilant about your weight. Combining a healthier diet and more activity is the best way to lose weight and keep it off for the long term. If you take weight-loss medications, you'll probably regain weight when you stop taking them. You might even regain weight after weight-loss surgery if you continue to overeat or eat foods laden with fat and calories.
Take your weight loss and weight maintenance one day at a time and surround yourself with supportive resources to help ensure your success. Find a healthier way of living that you can stick with for the long term.

References

1.     Defining overweight and obesity. Centers for Disease Control & Prevention. http://www.cdc.gov/obesity/defining.html. Accessed March 14, 2012.

2.     Bope ET, et al. Conn's Current Therapy. Philadelphia, Pa.: Saunders Elsevier; 2012. http://www.mdconsult.com/books/about.do?eid=4-u1.0-B978-1-4377-0986-5..C2009-0-38984-9--TOP&isbn=978-1-4377-0986-5&about=true&uniqId=236797353-5. Accessed March 14, 2012.

3.     Bray GA. Etiology and natural history of obesity. http://www.uptodate.com/index. Accessed March 14, 2012.

4.     Health care guideline: Prevention and management of obesity (mature adolescents and adults). Bloomington, Minn.: Institute for Clinical Systems Improvement. http://www.icsi.org/obesity/obesity_3398.html. Accessed Feb. 7, 2012.

5.     Understanding adult obesity. National Institute of Diabetes and Digestive and Kidney Diseases. http://www.win.niddk.nih.gov/publications/understanding.htm. Accessed March 15, 2012.

6.     Bray GA. Overview of therapy for obesity in adults. http://www.uptodate.com/index. Accessed March 14, 2012.

7.     The practical guide: Identification, evaluation, and treatment of overweight and obesity in adults. U.S. Department of Health and Human Services. http://www.nhlbi.nih.gov/guidelines/obesity/. Accessed March 15, 2012.

8.     Donnelly JE, et al. American College of Sports Medicine position stand: Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Medicine & Science in Sports & Exercise. 2009;41:459.

9.     Sacks F, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. New England Journal of Medicine. 2009;360:859.

10.                        Andrews RA, et al. Surgical management of severe obesity. http://www.uptodate.com/index. Accessed March 14, 2012.

11.                        Najm W, et al. Herbals used for diabetes, obesity, and metabolic syndrome. Primary Care. 2010;37:237.

12.                        Cho SH, et al. Acupuncture for obesity: A systematic review and meta-analysis. International Journal of Obesity. 2009;33:183.

13.                        Completed safety review: Xenical/Alli (Orlistat) and severe liver injury. U.S. Food and Drug Administration. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213038.htm. Accessed Feb. 16, 2011.

14.                        Sarwer DB, et al. A review of the relationships between extreme obesity, quality of life, and sexual function. Obesity Surgery. 2012;22:668.

15.                        Bray GA. Health hazards associated with obesity in adults. http://www.uptodate.com/index. Accessed March 14, 2012.

16.                        FDA expands use of banding system for weight loss. U.S. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm245617.htm. Accessed Feb. 7, 2012.

17.                        Belviq (prescribing information). San Diego, Calif.: Arena Pharmaceuticals; 2012. http://invest.arenapharm.com. Accessed June 29, 2012.

18.                        FDA approves Belviq to treat some overweight or obese adults. U.S. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm309993.htm. Accessed July 23, 2012.

19.                        FDA approves weight-management drug Qsymia. U.S. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm. Accessed July 18, 2012.

20.                        Qsymia (prescribing information). Mountain View, Calif.: Vivus Inc.; 2012. http://www.vivus.com/products. Accessed July 18, 2012.

21.                        Publication in Federal Register tomorrow moves Belviq (lorcaserin) closer to launch. Eisai, Inc. http://us.eisai.com/view_press_release.asp?ID=167&press=401. Accessed May 8, 2013.

Causes

At an individual level, a combination of excessive caloric intake and a lack of physical activity is thought to explain most cases of obesity. A limited number of cases are due primarily to genetics, medical reasons, or psychiatric illness. In contrast, increasing rates of obesity at a societal level are felt to be due to an easily accessible and palatable diet, increased reliance on cars, and mechanized manufacturing.
A 2006 review identified ten other possible contributors to the recent increase of obesity: (1) insufficient sleep, (2) endocrine disruptors (environmental pollutants that interfere with lipid metabolism), (3) decreased variability in ambient temperature, (4) decreased rates of smoking, because smoking suppresses appetite, (5) increased use of medications that can cause weight gain (e.g., atypical antipsychotics), (6) proportional increases in ethnic and age groups that tend to be heavier, (7) pregnancy at a later age (which may cause susceptibility to obesity in children), (8) epigenetic risk factors passed on generationally, (9) natural selection for higher BMI, and (10) assortative mating leading to increased concentration of obesity risk factors (this would not necessarily increase the number of obese people, but would increase the average population weight). While there is substantial evidence supporting the influence of these mechanisms on the increased prevalence of obesity, the evidence is still inconclusive, and the authors state that these are probably less influential than the ones discussed in the previous paragraph.
Diet-
The per capita dietary energy supply varies markedly between different regions and countries. It has also changed significantly over time. From the early 1970s to the late 1990s the average calories available per person per day (the amount of food bought) has increased in all parts of the world except Eastern Europe. The United States had the highest availability with 3,654 calories per person in 1996. This increased further in 2003 to 3,754. During the late 1990s Europeans had 3,394 calories per person, in the developing areas of Asia there were 2,648 calories per person, and in sub-Saharan Africa people had 2,176 calories per person. Total calorie consumption has been found to be related to obesity.
The widespread availability of nutritional guidelines has done little to address the problems of overeating and poor dietary choice. From 1971 to 2000, obesity rates in the United States increased from 14.5% to 30.9%. During the same period, an increase occurred in the average amount of calories consumed. For women, the average increase was 335 calories per day (1,542 calories in 1971 and 1,877 calories in 2004), while for men the average increase was 168 calories per day (2,450 calories in 1971 and 2,618 calories in 2004). Most of these extra calories came from an increase in carbohydrate consumption rather than fat consumption. The primary source of these extra carbohydrates are sweetened beverages, which now account for almost 25 percent of daily calories in young adults in America. Consumption of sweetened drinks is believed to be contributing to the rising rates of obesity.
As societies become increasingly reliant on energy-dense, big-portion, fast-food meals, the association between fast-food consumption and obesity becomes more concerning. In the United States consumption of fast-food meals tripled and calorie intake from these meals quadrupled between 1977 and 1995.
Agricultural policy and techniques in the United States and Europe have led to lower food prices. In the United States, subsidization of corn, soy, wheat, and rice through the U.S. farm bill has made the main sources of processed food cheap compared to fruits and vegetables.
Obese people consistently under-report their food consumption as compared to people of normal weight. This is supported both by test of people carried out in a calorimeter rooms and by direct observation.
-Sedentary lifestyle
A sedentary lifestyle plays a significant role in obesity. Worldwide there has been a large shift towards less physically demanding work, and currently at least 60% of the world's population gets insufficient exercise. This is primarily due to increasing use of mechanized transportation and a greater prevalence of labor-saving technology in the home. In children there appears to be declines in levels of physical activity due to less walking and physical education. World trends in active leisure time physical activity are less clear. The World Health Organization indicates that people worldwide are taking up less active recreational pursuits, while a study from Finland found an increase and a study from the United States found leisure-time physical activity has not changed significantly.
In both children and adults there is an association between television viewing time and the risk of obesity. A 2008 meta-analysis found that 63 of 73 studies (86%) showed an increased rate of childhood obesity with increased media exposure, with rates increasing proportionally to time spent watching television.
-Genetics
Like many other medical conditions, obesity is the result of an interplay between genetic and environmental factors. Polymorphisms in various genes controlling appetite and metabolism predispose to obesity when sufficient calories are present. As of 2006 more than 41 of these sites have been linked to the development of obesity when a favorable environment is present. The percentage of obesity that can be attributed to genetics varies, depending on the population examined, from 6% to 85%.
Obesity is a major feature in several syndromes, such as Prader-Willi syndrome, Bardet-Biedl syndrome, Cohen syndrome, and MOMO syndrome. (The term "non-syndromic obesity" is sometimes used to exclude these conditions.) In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single point DNA mutation.
Studies that have focused upon inheritance patterns rather than upon specific genes have found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.
The thrifty gene hypothesis postulates that certain ethnic groups may be more prone to obesity in an equivalent environment. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would be more likely survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This is the presumed reason that Pima Indians, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.
-Infectious agents
The study of the effect of infectious agents on metabolism is still in its early stages. Gut flora has been shown to differ between lean and obese humans. There is an indication that gut flora in obese and lean individuals can affect the metabolic potential. This apparent alteration of the metabolic potential is believed to confer a greater capacity to harvest energy contributing to obesity. Whether these differences are the direct cause or the result of obesity has yet to be determined unequivocally.
An association between viruses and obesity has been found in humans and several different animal species. The amount that these associations may have contributed to the rising rate of obesity is yet to be determined.

Pathophysiology

Flier summarizes the many possible pathophysiological mechanisms involved in the development and maintenance of obesity. This field of research had been almost unapproached until leptin was discovered in 1994. Since this discovery, many other hormonal mechanisms have been elucidated that participate in the regulation of appetite and food intake, storage patterns of adipose tissue, and development of insulin resistance. Since leptin's discovery, ghrelin, insulin, orexin, PYY 3-36, cholecystokinin, adiponectin, as well as many other mediators have been studied. The adipokines are mediators produced by adipose tissue; their action is thought to modify many obesity-related diseases.
Leptin and ghrelin are considered to be complementary in their influence on appetite, with ghrelin produced by the stomach modulating short-term appetitive control (i.e. to eat when the stomach is empty and to stop when the stomach is stretched). Leptin is produced by adipose tissue to signal fat storage reserves in the body, and mediates long-term appetitive controls (i.e. to eat more when fat storages are low and less when fat storages are high). Although administration of leptin may be effective in a small subset of obese individuals who are leptin deficient, most obese individuals are thought to be leptin resistant and have been found to have high levels of leptin. This resistance is thought to explain in part why administration of leptin has not been shown to be effective in suppressing appetite in most obese people.

A graphic depiction of a leptin molecule
While leptin and ghrelin are produced peripherally, they control appetite through their actions on the central nervous system. In particular, they and other appetite-related hormones act on the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the melanocortin pathway being the most well understood. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively.
The arcuate nucleus contains two distinct groups of neurons. The first group coexpresses neuropeptide Y (NPY) and agouti-related peptide (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH. The second group coexpresses pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and has stimulatory inputs to the VMH and inhibitory inputs to the LH. Consequently, NPY/AgRP neurons stimulate feeding and inhibit satiety, while POMC/CART neurons stimulate satiety and inhibit feeding. Both groups of arcuate nucleus neurons are regulated in part by leptin. Leptin inhibits the NPY/AgRP group while stimulating the POMC/CART group. Thus a deficiency in leptin signaling, either via leptin deficiency or leptin resistance, leads to overfeeding and may account for some genetic and acquired forms of obesity.