Obesity genetic determinants

Primary increases of VLDL probably reflect a number of genetic determinants and are worsened by factors that increase the rate of VLDL secretion from liver, ie, obesity, alcohol, diabetes, and estrogens. A major indication for treatment is the presence of atherosclerosis in the patient or the patient s family. Treatment includes weight reduction, restriction of all types of dietary fat, and avoidance of alcohol. Fibrates or niacin usually produce further reduction in triglyceride levels if dietary measures are not sufficient. Marine omega fatty acids may also be of value. 

When leptin was first discovered, there was great hope that, as in the obese mouse, human obesity (see Chapter 6) might be due to a failure of leptin synthesis or secretion, and that administration of synthetic leptin might be a useful treatment for severe obesity. However, most obese people secrete more leptin than lean people (because they have more adipose tissue), and it is likely that the problem is due not to lack of leptin, but rather to a loss of sensitivity of the leptin receptors. Only in a very small number of people has obesity been found to be genetically determined by a mutation in the leptin gene. 

It would be very interesting to know to what extent the genetic obesity which can be produced by selective breeding in laboratory rodents is a model relevant to human obesity. This is not an easy question to answer. Human obesity tends to run in families, but this does not prove that it is genetically determined. The distribution of body fat is more similar in human identical twins than in dizygotic twins, but the total amount of fat in identical twins reared apart seems to be determined more by environment than heredity. 

Genetic factors appear to be the primary determinants of obesity in some individuals, whereas environmental factors are more important in others. The specific gene that codes for obesity is unknown there is probably more than one gene. 

Genetic mechanisms play a primary role in determining body weight. Obesity behaves as a complex polygenic disease, involving interactions between multiple genes and the environment. 

Human obesity and hypertension have strong genetic as well as environmental determinants. Several observations show associations of 02- and 03-adrenoceptor polymorphisms with hypertension and obesity, although these findings have not been confirmed. In addition, relationships between adrenoceptor polymorphisms, plasma... 

It is now widely accepted that obesity is a disease in its own right, with clear genetic as well as environmental determinants (Jung 1997). As a report from the Royal College of Physicians of London emphasises Obesity must therefore be considered a serious medical issue rather than a perversity of current fashion (Physicians 1998). Obesity is clearly a disease, in the same sense as hypertension and atherosclerosis are diseases, and constitutes a major health problem (Bray 2004). 

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