This diagram represents the pathways by which leptin and ghrelin may have effect on energy balance in humans. This schematic drawing shows the pathways by which leptin and ghrelin may reach the hypothalamus, in order to have an effect on food intake and body weight. Leptin is secreted by adipose tissue and the stomach secretes ghrelin. Both hormones may enter the brain through the bloodstream (long arrow with straight line). In addition, ghrelin and gastric leptin may reach the hypothalamus through the vagal nerve and nucleus tractus solitarus (short arrows with straight line). In addition, central ghrelin may affect the energy centre in the hypothalamus (curved arrow). Leptin and ghrelin both stimulate (+) and suppress (–) hypothalamic neurons containing various neuropeptides, resulting in anorexic or orexic effects on energy balance (open arrows). Studies on the effect of leptin on circulating ghrelin levels produced conflicting results; whether ghrelin has influence on circulating leptin levels has not yet been demonstrated (curved arrows with dashed line). AgRP, agouti-related protein; BDNF, brain-derived neurotropic factor; CART, cocaine- and amphet- amine-regulated transcript; CRH, corticotropin- releasing hormone; GALP, galanin-like peptide; MCH, melanin-concentrating hormone; NPY, neuropeptide Y; NT, neurotensin; POMC, pro- opiomelanocortin. [8,9]

Let us have a quick review: the hormone leptin acts in your brain to adjust the expression of several chemicals from your hypothalamus. These chemicals maintain the balance when leptin from your fat cells, alerts your brain that you have had enough to eat. What happens next is that you become less hungry. [4,5]

The transmitter that maintains the relationship between fat tissue and the brain is known as an endocannabinoid, which translates the information as to the amount of body fat needed to deal with energy requirement. Think of leptin as a fat cell thermostat, active in the fat depots, while monitoring your energy maintenance system. [3,4]

Leptin does this by modifying the appetite-regulating chemicals called peptides, which are either appetite stimulating (orexigenic) or appetite suppressing (anorexigenic). Leptin also suppresses a liver enzyme that converts unsaturated fats into monounsaturated fats burning fat as energy.[3,4]

The balance and communication between these two systems sets a limit on food intake and growth hormone release. An impairment of this equilibrium results in disorders of feeding behavior such as weight gain or weight loss (cachexia). Neither is very desirable. If leptin is so useful, what about getting leptin shots?

Unfortunately, doctors can’t give someone a leptin shot to make them stop eating, since in severely obese people, unlike mice, hormones seem to work differently. In genetically altered mice, without the receptor for leptin, injecting leptin will only partially correct the defect reversing their obesity. This indicates that other factors play supporting roles. Leptin corrects insulin resistance, or diabetes, in mice that lack fat tissue (a condition called lipodystrophy). Scientists have tried leptin replacement therapy in lipodystrophic humans with good results. [3,5]

People who are out of control with their eating may have become leptin-insensitive. In reality, when they are full, they don’t stop eating. They have become resistant to their own leptin effects. If leptin is not working then the enzyme mentioned earlier rises and more fat is stored in the liver. Women seem to suffer from this problem more than men. But remember that most of these genetic effects have been bred into our species over time. You can modify your genetics. [5,6]

Obesity:

Obesity is a disorder, which involves excess amount of body fat. It’s not just a cosmetic concern but it also leads to a lot of health problems like diabetes, heat disease and high blood pressure. Being extremely obese means you are especially likely to have health problems related to your weight. [4]

The good news is that even modest weight loss can improve or prevent the health problems associated with obesity. Dietary changes, increased physical activity and behavior changes can help you lose weight. Prescription medications or weight-loss surgery also may be options for treating obesity. [8]

Obesity is likely when an individual's body mass index (BMI) is 30 or higher. Your body mass index is calculated by dividing your weight in kilograms (kg) by your height in meters (m) squared. [15]

BMI	Weight status
Below 18.5	Underweight
18.5-24.9	Normal
25.0-29.9	Overweight
30.0-34.9	Obese (Class I)
35.0-39.9	Obese (Class II)
40.0 and higher	Extreme obesity (Class III)

BMI is a reasonable estimate of body fat but it does not directly measure our body fat. Some people such as muscular athletes will have a BMI is the obese category even thought they don’t have excess body fat. Your health care provider will decide this when u wish to get your treatment done. [20,21]

Causes of obesity:

Regardless of the genetic and hormonal influences in body weight, obesity also occurs when you take in more calories than you burn through exercise and normal daily activities. These excess calories are stored as fat, obesity usually results from a combination of causes and contributing factors including:

Inactivity: If you are leading a sedentary lifestyle it is very easy to add extra calories to your body due to lack of exercise. This will be stored as fat. [10]

Unhealthy diet and eating habits: Having a diet that's high in calories, lacking in fruits and vegetables, full of fast food, missing breakfast, and laden with high-calorie beverages and oversized portions all contribute to weight gain.[10]

Pregnancy: During pregnancy, a woman's weight necessarily increases. Some women find this weight difficult to lose after the baby is born. This weight gain may contribute to the development of obesity in women. [10]

Lack of sleep: Too little sleep can cause changes in hormones that increase your appetite. You may also crave foods high in calories, which can contribute to weight gain.[10]

Certain medications: Some medications can lead to weight gain if you don't compensate through diet or activity. These medications include some antidepressants, anti-seizure medications, diabetes medications, antipsychotic medications, corticosteroids and beta blockers.[11]

Medical problems: Obesity can sometimes be traced to a medical cause, such as Prader-Willi syndrome, Cushing's syndrome, and other diseases and conditions. Some medical problems, such as arthritis, can lead to decreased activity, which may result in weight gain. A low metabolism is unlikely to cause obesity, as is having low thyroid function. [10]

Risk factors:

Obesity occurs when you eat and drink more calories than you burn through exercise and normal daily activities. Your body stores these extra calories as fat. Obesity usually results from a combination of causes and contributing factors, including:

Genetics: Genes may have an affect on the amount of body fat that is stored and where it is distributed. It also plays a role in how efficiently your body converts food into energy and how your body burns calories during exercise. Even when someone has a genetic predisposition, environmental factors ultimately make you gain more weight. [11]

Family lifestyle: Obesity tends to run in families. That's not just because of genetics. Family members tend to have similar eating, lifestyle, and activity habits. If one or both of your parents are obese, your risk of being obese is increased. [11]

Inactivity: If you're not very active, you don't burn as many calories. With a sedentary lifestyle, you can easily take in more calories every day than you burn off through exercise and normal daily activities. [14]

Unhealthy diet and eating habits: A diet that's high in calories, lacking in fruits and vegetables, full of fast food, missing breakfast, and laden with high-calorie beverages and oversized portions contributes to weight gain. [13]

Quitting smoking: Quitting smoking is often associated with weight gain. And for some, it can lead to enough weight gain that the person becomes obese. In the long run, however, quitting smoking is still a greater benefit to your health than continuing to smoke.[16]

Pregnancy.During pregnancy, a woman's weight necessarily increases. Some women find this weight difficult to lose after the baby is born. This weight gain may contribute to the development of obesity in women. [16]

Lack of sleep: Not getting enough sleep or getting too much sleep at night can cause changes in hormones that increase your appetite. You may also crave foods high in calories and carbohydrates, which can contribute to weight gain. [2]

Certain medications: Some medications can lead to weight gain if you don't compensate through diet or activity. These medications include some antidepressants, anti-seizure medications, diabetes medications, antipsychotic medications, steroids, and beta-blockers. [2]

Age: Obesity can occur at any age, even in young children. But as you age, hormonal changes and a less active lifestyle increase your risk of obesity. In addition, the amount of muscle in your body tends to decrease with age. This lower muscle mass leads to a decrease in metabolism. These changes also reduce calorie needs and can make it harder to keep off excess weight. If you don't control what you eat and consciously become more physically active as you age, you'll likely gain weight. [17]

Social and economic issues: Certain social and economic issues may be linked to obesity. You may not have safe areas to exercise, you may not have been taught healthy ways of cooking or you may not have money to buy healthier foods. In addition, the people you spend time with may influence your weight — you're more likely to become obese if you have obese friends or relatives. [23]

Medical problems: Obesity can rarely be traced to a medical cause, such as Prader-Willi syndrome, Cushing's syndrome, and other diseases and conditions. Some medical problems, such as arthritis, can lead to decreased activity, which may result in weight gain. [23]

Even if you have one or more of these risk factors, it doesn't mean that you're destined to become obese. You can counteract most risk factors through diet, physical activity and exercise, and behavior changes.

Side effects of obesity:

Tests, diagnosis, and treatment for diabetes should be done as soon as possible as there are many side effects to it, diseases that are hard to be cured. The most prevalent diseases due to obesity are:

More than 65 million adults and 10 million children suffer from obesity, considered one of the leading causes of life-threatening diseases. Being morbidly obese can compromise your health, shorten your life, and even cause death. If you are overweight, the probabilities of developing heart disease, diabetes, and high blood pressure increase significantly. Here are the top 10 obesity-related diseases.

1. High Blood Pressure: High blood pressure is the primary cause of death among Americans older than 25. About 75 million people suffer from high blood pressure or hypertension, which is a major risk factor for heart disease. Blood pressure tends to increase with weight gain and age. It is not known why obesity is a major cause of high blood pressure. However, research has shown that obese patients displayed an increase in blood volume and arterial resistance. For people who are overweight and have high blood pressure, losing as little as 8 pounds can help reduce blood pressure to a safe level. [12]

2. Diabetes: Obesity is considered one of the most significant factors in the development of insulin resistance, and insulin resistance can lead to type 2 diabetes According to the World Health Organization, more than 90 percent of diabetes patients worldwide have type 2 diabetes. Being overweight or obese contributes to the development of diabetes by making cells more resistant to the effects of insulin. A weight loss of 15-20 pounds can help you decrease your risk of developing type 2 diabetes. [15]

3. Heart Disease: According to the American Heart Association, obesity is a major risk factor for developing coronary heart disease, which can lead to a heart attack or stroke. People who are overweight are at a greater risk of suffering a heart attack before the age of 45. Obese adolescents have a greater chance of having a heart attack before the age of 35 than non-obese adolescents. If you are overweight, losing 10-15 pounds can reduce your risk of developing heart disease. If you exercise regularly, the risk of developing heart disease falls even more. [15]

4. High Cholesterol levels: High cholesterol is one of the leading causes of heart attacks. Cholesterol is transported through your blood in two ways: the low –density lipoprotein (LDL), which transports cholesterol to the cells that need it, and the high-density lipoprotein (HDL), which is the healthy cholesterol that reduces your risk for heart attack. Having high LDL levels raises your risk of having heart disease by 20 percent. Losing 11-20 pounds can help you significantly reduce your cholesterol level. [15]

5. Cancer: A study by the American Heart Association found that being overweight increases your chances for developing cancer by 50 percent. Women have a higher risk of developing cancer if they are more than 20 pounds overweight. Regular exercise and a weight loss of as little as 12 pounds can significantly decrease the risk. [16]

6. Infertility: Being obese can cause changes in the hormonal levels of women, which can result in ovarian failure. Women who are 15-25 pounds overweight are at a higher risk of suffering from infertility and ovarian cancer. Our bodies need to be at an appropriate weight to produce the right amount of hormones and regulate ovulation and menstruation. Don’t think men are immune to infertility. Overweight men have a greater chance of developing motility and a lower sperm count. Shedding 12-14 pounds can help you lower the risks. [16]

7. Back Pain: Obesity is one the contributing factors of back and joint pain. Excessive weight can cause injury to the most vulnerable parts of the spine, which carries the body’s weight. When it has to carry excess weight, the odds of suffering from a spinal injury or structural damage increase. Being overweight also raises the risk of developing osteoporosis, lower back pain, arthritis, and osteoarthritis. Losing 10-15 pounds can help you decrease the risk of developing these problems. [17]

8. Skin Infections: Obese and overweight individuals may have skin that folds over on itself. These creased areas can become irritated from the rubbing and sweating, which can lead to skin infections. [15]

9. Ulcers: According to a study by the National Institutes of Health (NIH), obesity can be a contributing factor to the development of gastric ulcers. Gastric ulcers occur when there is an imbalance between the amount of hydrochloric acid that is secreted and the enzyme pepsin. Overweight men are at a greater risk of developing gastric ulcers than women. A weight loss of as little as 7 pounds can help reduce the risk. [16]

10. Gallstones: Being severely overweight increases the risk of developing gallstones, especially in women. Gallstones are caused when the liver releases excessive amounts of bile, which is stored in the gallbladder. Gallstones are more common in older women and those with a family history of gallstones. Losing 4-9 pounds reduces the risk of developing gallstones. Moderate exercise also can help lower your risk. [16]

What you can do in the meantime:

If you have time before your scheduled appointment, you can help prepare for the appointment by keeping a diet diary for two weeks prior to the appointment and by recording how many steps you take in a day by using a step counter (pedometer).

You can also begin to make choices that will help you start to lose weight, including:

Starting to make healthy changes in your diet, such as eating more fruits, vegetables and whole grains and reducing portion sizes. Focus on achievable, enjoyable changes. Eat breakfast.

Tracking how much you're eating or drinking each day so that you get a sense of how many calories you're taking in. It's easy to underestimate how many calories you actually take in every day. Bring this information with you to your appointment. [15,16]

Beginning to increase your activity level. Try to get up and move around your home more frequently. Start gradually if you aren't in good shape or aren't used to exercising. Even a 10-minute daily walk can help. If you have any health conditions, or if you're a man over age 40 or a woman over age 50, talk to your doctor or health care provider before you start a new exercise program. [18]

Tests and diagnosis:

If your BMI is in the overweight or obese range, your health care provider will typically review your health history in detail, perform a physical exam and recommend some tests.

Your weight history must be reviewed such as weight loss efforts, exercise habits and eating patterns. Health problems of the patient is check like diabetes or high blood pressure. BMI is the first main thing that should be checked when a person comes for an obesity test. Waist circumference of the patient is measured. Women with a waist circumference of more than 35inches and men with a waist circumference of more than 40 inches have more health risks that people with smaller waist measurements. Blood tests are done, the test may include a cholesterol test, liver function tests, fasting glucose, a thyroid test and others, depending on your health situation. Your doctor may also recommend certain heart tests, such as an electrocardiogram. [19-21]

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 dietitian, behaviourtherapist 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 — 3 to 5 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 6 to 10 pounds (2.7 to 4.5 kg) for your health to begin to improve. However, the more weight you lose, the greater the benefits. [20,21]

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

· Exercise and activity

· Behaviour change

· Prescription weight-loss medications

· Weight-loss surgery [16,20]

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 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.

Plan to participate in a comprehensive weight-loss program for at least six months and in the maintenance phase of a program for at least a year to boost your odds of weight loss success.

There is no best weight-loss diet. Choose one that includes healthy foods that you feel will work for you. Dietary changes to treat obesity include:

A reduced-calorie diet. The key to weight loss is reducing how many calories you take in. You and your health care providers can review your typical eating and drinking habits to see how many calories you normally consume and where you can cut back. You and your doctor can decide how many calories you need to take in each day to lose weight, but a typical amount is 1,200 to 1,500 calories for women and 1,500 to 1,800 for men. [20]

Adopting a healthy-eating plan. To make your overall diet healthier, eat more plant-based foods, such as fruits, vegetables and whole-grain carbohydrates. Also emphasize lean sources of protein — such as beans, lentils and soy — and lean meats. If you like fish, try to include fish twice a week. Limit salt and added sugar. Stick with low-fat dairy products. Eat small amounts of fats, and make sure they come from heart-healthy sources, such as nuts and olive, canola, and nut oils. [20]

Restricting certain foods. Certain diets limit the amount of a particular food group, such as high-carbohydrate or full-fat foods. Ask your doctor which diet plans have been found effective and which might be helpful for you. Drinking sugar-sweetened beverages is a sure way to consume more calories than you intended, and limiting these drinks or eliminating them altogether is a good place to start cutting calories. [21]

Meal replacements. These plans suggest that you replace one or two meals with their products — such as low-calorie shakes or meal bars — and eat healthy snacks and a healthy, balanced third meal that's low in fat and calories. In the short term, this type of diet can help you lose weight. Keep in mind that these diets likely won't teach you how to change your overall lifestyle, though, so you may have to keep this up if you want to keep your weight off. [21]

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.

To boost your activity level:

Exercise:

People who are overweight or obese need to get at least 150 minutes a week of moderate-intensity physical activity to prevent further weight gain or to maintain the loss of a modest amount of weight. To achieve more significant weight loss, you may need to exercise 300 or more minutes a week. You probably will need to gradually increase the amount you exercise as your endurance and fitness improve. To make your own exercise goal more doable, break it up into several sessions throughout the day, doing just 10 minutes at a time. Exercising with a partner can make this more fun and help you maintain your motivation. [23]

Increase your daily activity.

Even though regular aerobic exercise is the most efficient way to burn calories and shed excess weight, any extra movement helps burn calories. Making simple changes throughout your day can add up to big benefits. Park farther from store entrances, rev up your household chores, garden, get up and move around periodically, and wear a pedometer to track how many steps you actually take over the course of a day. [24,25]

In some cases, weight loss surgery such as bariatric surgery is an option. It can only be done if your BMI is 35 or more. There is gastric bypass surgery, laparoscopic adjustable gastric banding, gastric switch and Biliopancreatic diversion with duodenal switch.

Behaviour changes:

A behaviour modification program can help you make lifestyle changes and 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. Everyone is different and has different obstacles to managing weight, such as a lack of time to exercise or late-night eating. Tailor your behavior changes to address your individual concerns.

Behaviour modification, sometimes called behaviour therapy, can include:

Counseling:

Therapy or interventions with trained mental health or other professionals can help you address emotional and behavioural issues related to eating. Therapy can help you understand why you overeat and learn healthy ways to cope with anxiety. You can also learn how to monitor your diet and activity, understand eating triggers, and cope with food cravings. Counselling may be available by telephone, email or Internet-based programs if travel is difficult. Therapy can take place on both an individual and group basis. More-intensive programs — those that include 12 to 26 sessions a year — may be more helpful in achieving your weight-loss goals. [20,21]

Support groups:

You can find camaraderie and understanding in support groups where others share similar challenges with obesity. Check with your doctor, local hospitals or commercial weight-loss programs for support groups in your area, such as Weight Watchers. [20]

Preventing weight gain after obesity:

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. Aim for 200 to 300 minutes a week. 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. [21,23]

You may always have to remain vigilant about your weight. Combining a healthier diet and more activity in a practical and sustainable manner 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. [20]

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. [22]

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