"The best measure of a man's honesty isn't his income tax return. It's the zero adjust on his bathroom scale."

-- Arthur C. Clarke

Obesity is defined as increased body weight caused by excessive accumulation of fat. Due to centuries of under nutrition, the human body regulation mechanisms seem to be biased towards fat preservation rather than elimination. The shift towards obesity has occurred in many countries in less than one generation. Obesity is now regarded as a global epidemic affecting both adults and children, and is associated with significant morbidity and mortality. Prevalence of adult obesity is very high in the USA (33% in both genders), in oil-rich Arabian countries (30% in males and 40 % in females) and in European Union (up to 25% in both genders).

An understanding of the pathways controlling appetite, satiety and food intake is essential for gaining an insight into the development of obesity and also for the development of diagnostic tests and therapeutic agents for use in the clinical management of this condition. The aim of contemporary research is to understand the molecular and other control mechanisms which the body uses to regulate its storage of energy in the form of fat. Obesity is associated with an increased risk of numerous conditions including type 2 diabetes, metabolic syndrome, hypertension, cardiovascular diseases, osteoarthritis and cancer. The lowest all-cause mortality occurs in people with a body mass index, BMI, between 23.0 and 27.0 according to data from the USA and China.

Over the last few years, the exact chemistry of human genes, the human genome, has been elucidated. Supportive evidence for the role of leptin in body weight related problems has been found. Several other loci of varying significance were detected across the genome. Obesity has been shown to be heritable, but most studies predate the onset of the "obesity epidemic" that has been rampant over the last twenty years. Professor Wardle and her colleagues at University College London have recently carried out twin analyses of body mass index (BMI) and waist circumference (WC) in a UK sample of 5092 twin pairs aged 8-11 years.0801 There was a significant genetic effect of 40%.

The FTO gene has consistently been associated with obesity across multiple populations. However, to date it was not known whether the association between genetic variation in FTO and obesity is mediated through effects on energy intake or energy expenditure. Wardle's group0802 have recently  demonstrated (July 2008) that the commonest known FTO obesity-risk gene is likely to exert at least some of its effects by influencing appetite. Those with this obesity-risk gene do not have their appetite satiated easily so that they have a genetic tendency which tends to make them eat more.

Leptin, a hormone-like chemical secreted by adipose (fat) tissue, correlates strongly with obesity. Over the last decade or more research using both mouse and human genetic models has elucidated the critical role of the leptin pathway in the hypothalamus, in regulating mammalian energy balance.

Adrenal type hormones that stimulate the sympathetic nervous system have not thus far become a basis of drugs for the treatment of obesity, but they offer perspectives on obesity drug discovery, and the mechanism of energy expenditure. These hormones selectively stimulate fat oxidation in rodents and humans. They improve insulin sensitivity and reduce body fat whilst preserving lean body mass. Novel anti-obesity drugs that improve insulin sensitivity and reduce mainly body fat are required. Leptin resembles some sympathetic nervous system agonists in that it increases fat oxidation, energy expenditure and insulin sensitivity.

It is likely that many genes contribute to obesity and appetite, each making a small contribution, but together creating a substantial effect. There is increased understanding of the central pathways by which known neurotransmitters affect food intake. Despite the discovery of new genes and hormones such as leptin, and of other new mechanisms, the prevention and treatment of obesity remains an escalating problem.

 

How does body weight affect fertility?

 

www.cancer.org/downloads/STT/Cancer_Statistics_Combined_2007. Ppt

If you are overweight your fertility will be reduced. This is true for both men and women. It is unclear whether it is the weight that is an independent factor for women or whether other factors such as polycystic ovary syndrome (PCOS -Q7.2) result in both the infertility and excess weight. At the other extreme, if you are under your ideal weight you are more likely to have anovulation problems (Q9.17). The Body Mass Index (BMI) is a ratio used to compare your weight with your height. The BMI is calculated as indicated in Table 9.1.

 

Table 9.1  Calculating your Body Mass Index.

 

     BMI = Weight (Kg) / Height (m)2.

 

Your BMI should be between 20 and 24. If your BMI is less than 20 you are underweight. You should lose weight if your BMI is between 25 and 29. You are considered to be medically obese if your BMI is 30 or more and you would be regarded as very obese if your BMI is greater than 40.

Table 9.1

Weight Kg and

(st / lb)

 

Height in metres and (ft ins)

Height (m2)

BMI

49

(7st 110lb)

1.63

(5ft 4ins)

1.632

18 (49 / 1.632)

61

(9st 9lb)

1.58

(5ft 2ins)

1.582

24 (61 / 1.582)

90

(14st 2lb)

1.68

(5ft 6ins)

1.682

32 (90 / 1.682)

106

(16st 10lb)

1.55

(5ft 1ins)

1.552

44 (106 / 1.552)

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How can I lose weight?

The incidence of obesity is increasing.

Our body weight will remain steady if the amount of energy we obtain from our food is equal to the amount of energy we expend. If we take in more energy in the food that we eat than we burn up then we will gain weight and conversely if we burn up more energy than we obtain from our food then we will lose weight.

Energy is measured in calories. A calorie is the amount of energy required to raise the temperature of one millilitre of water by one degree centigrade. An average woman will use about 1800 to 2600 thousand calories each day. A kilocalorie (kcal) is a thousand calories. There appears to be a misquotation about the units of energy content of food. It is often said that a banana contains 100 calories. It contains 100 thousand calories (100 kcal).

As an approximate guide 400 kcals will e quate to an ounce of body fat. Let us provide an example. A woman is keeping her weight steady and then changes habit and eats one less chocolate biscuit (100 kcals) each day. In one week, her calorie intake will be reduced by 700 kcal and in a 30 day month 100 x 30 = 3,000 kcals. As 400 kcals e quates to an ounce of body fat, she would lose 3,000/400 = 7.5 ozs each month leading to a weight loss of 7.5 x 12 ozs = 90ozs or 90/16 = 5.6lbs in one year (2.5kgs).

The energy we burn in a day depends on our basal metabolic rate combined with the energy used as we work and exercise. Sadly, for those of us doing sedentary work, our brains do not consume additional energy even though they increase our mental output. The author may spend a lot of time working on his computer but this does not burn away calories.

Dieting and Exercise:

If we are honest with ourselves, most of us who have difficulty keeping our body weight down eat too much. There are clinical studies that have proven this. The simple answer to the question 'How can I lose weight' is that you must consume less calories than you use. You can lose weight by reducing the amount of calories you eat in your diet and by increasing the amount of exercise that you undertake. Increasing your exercise is beneficial, not only because it increases your energy expenditure, but also because there will be an increase in proportion of muscle and this increases your basal metabolic rate.

There is some debate about the best form of diet to follow when weight loss is required. Carbohydrates, protein and fat each provide energy sources for the body and there has been an assumption that a carbohydrate calorie is e quivalent to a protein or fat calorie. Most diets recommend reduction in total food intake and particularly of fat but there is an interesting deviation from this rule by a diet that strictly reduces carbohydrate intake whilst leaving virtual freedom in the amount of protein you eat (Atkins diet). From a theoretical point of view, it could be that reducing your carbohydrate intake and hence sugar absorption will reduce the amount of insulin released into the blood. Insulin converts sugar into body fat. Scientific studies are required to evaluate the relative benefits of these diets. Whichever diet you choose, a balanced diet with adequate vitamin requirements is essential for long-term health.

When you start a new weight reducing diet, do not be misled by dramatic changes in the first few days and weeks. A lot of food is present in the stomach and intestine. If you consume less food, the content of the intestine will be reduced leading to quick weight loss. If your basal metabolic rate is 2,500 kcals per day and you eat nothing then you would lose 2,500/400 (6.25) ozs of fat and serious problems can arise if you do not eat a sensible diet. If you were to keep to a 1500 kcal diet you would lose 1,000 kcals or 1000/400 (2.5ozs) per day or 75 ozs (4lb) in a month.

Clinical Causes of Body Weight Problems:

There are a few clinical situations that may confound the energy e quation. The thyroid gland produces hormones such as thyroxine that set our basal metabolic rate the rate that we consume energy at rest. Patients with an overactive thyroid have high levels of thyroxine and they tend to lose weight. Those with an under active thyroid will tend to gain weight.

In recent years, there has been an interest in insulin resistance (PCOS cause). Those with insulin resistance need to have increased levels of insulin to stop their blood sugar levels running to high. Insulin converts sugar into fat. This may explain why some patients with polycystic ovary syndrome tend to be obese (PCOS cause). It does not explain why some patients who have PCOS are not overweight even though they have increased insulin resistance. Those who are obese and have PCOS may lose weight with a drug called metformin (Q7.14).

Medical Treatment of Increased Body Weight:

Medical treatment, particularly with female hormones, is commonly blamed for weight increase and citation of medical texts used to justify these claims. These citations indicate that some patients gain weight on the treatment but they also say that others lose weight. Few of us are able to maintain a steady and desirable weight without watching our diet and most of us are in a state of weight loss or weight gain over the course of a few months. Most of us continue to gain weight at least until our fifties. Studies of body weight change with the combined oral contraceptive pill and with hormone replacement therapy have shown that overall there is no significant change in body weight attributable to them. There may be a redistribution of body fat with HRT; there could be an increase in breast tissue and reduction of the waistline.

Leptin is a hormone that regulates appetite and energy expenditure. Animals that are deficient in leptin tend to be obese. The majority of overweight people do not have leptin problems. Leptin can be manufactured and administered with the aim of causing weight loss. More needs to be known about the role of leptin before it could be considered as a potentially beneficial medication for the obese.

Orlistat (Xenical? - Roche) is a lipase inhibitor. Lipase is an enzyme that is secreted into the intestine to break down fat in our food. By reducing the lipase activity more fat passes through the intestine and is not absorbed. A potential problem with orlistat is that the stool may be greasy and some patients may report faecal incontinence at first. Appetite suppressing agents are not generally recommended for the obese as they tend to cause side effects. Diuretics are drugs that increase the amount of urine we produce and they reduce the amount of body fluid. They should not be used to reduce body weight. 

Sibutramine (Reductil - Knoll AG) is a medicine to help you lose weight. It works by making you feel satisfied with less food. It helps control how much you eat. By eating less, it should be easier for you to lose weight, even if you haven't been able to before. mainly works by making you feel more 'full' with less food (it reduces appetite and enhances satiety).

Sibutamine should not be taken if you are, or plan to be, pregnant.

Studies have shown that, on average, sibutramine plus a weight-reducing diet and exercise causes more weight loss than a weight-reducing diet and exercise alone. Some people lose up to 7% or more of their body weight within 6-12 months with the help of sibutramine. In others, it is less effective.

One reason why sibutramine may not work is that you may think that you can relax your weight-reducing diet, and the sibutramine will 'do it all'. This is not true. Sibutramine does not make you lose weight. It will only partially suppress your appetite. You still have to continue to eat a healthy weight-reducing diet, and to exercise more if possible.

It is only advised if you have had difficulty in losing weight over a three month trial with weight-reducing diet and exercise alone.

Your BMI (Body Mass Index - see below)

  • must be 30 or above, or
  • must be 27 or above, and you have a medical condition that would benefit from losing weight (such as diabetes).
  • You must lose at least 2 kg in weight at four weeks, and 5% of your initial weight by three months from starting sibutramine. If not, it should be stopped.
  • You must be between the ages of 18 and 65 years.
  • If you continue to lose weight, sibutramine can be continued for a maximum of one year.
  • You should not take sibutramine if you have: high blood pressure, heart disease, heart failure, peripheral vascular disease, arrhythmias (abnormal heart rhythms), or have had a stroke.
  • Most people have no side effects. Those that may occur include the following:

    • Constipation, dry mouth, and difficulty with sleeping are relatively common.
    • Your blood pressure and pulse may become raised. This is why your doctor will want to monitor your blood pressure if you take sibutramine. You will have to stop taking this medicine if your blood pressure or resting pulse rate increase after you start taking it.

Rimonabant(Acomplia-Sanofi-Aventis)

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, obesity/metabolic syndrome.

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