Obesity is caused by complex interaction of genetic and environmental factors. It is difficult to determine if genetics play a dominant role or environmental factors play the dominant role in causation of obesity. In general a favorable environment and a genetic susceptibility interact to cause obesity.

The actual causes of obesity are still not clear despite tremendous development in medical science, including understanding of molecular pathways which regulate energy balance in humans, an essential component in pathogenesis of obesity. The cause obesity seems to be simple, such as chronic and excess consumption of food (calories) than expenditure of energy. But this theory of chronic excess nutrient intake relative to the level of energy expenditure does not hold in every obese individual, which proves that there are several other causes of obesity than simple consumption of excess food than we need.

Genes vs. Environment in Obesity:

Obesity is seen among families, which proves that genetic factors play an important role in causation of obesity. The genetic inheritance of obesity is not Mendelian type and it is very difficult to differentiate the role of genetics and environmental factors.

Points in favor of role of genetics in causation of obesity includes the BMI of identical twins are similar, despite growing up in different environments, whereas the BMIs of dizygotic twins are different and resemblance of adoptees to their biologic parents than their adopted parents in terms of obesity.

Environmental factors play an important role in obesity, e.g. the recent increase in prevalence of obesity many countries such as Australia, United States is too rapid to be due to change in genetics. Although genes influence susceptibility to obesity in response to specific nutritional items, but generally environmental factors directly act to cause obesity. Environmental factors such as time spent in front of television, sleep deprivation, cultural factors and consumption of high fat diets can cause obesity, even if an individual is not genetically susceptible to obesity.

There are also reports that change in the normal gut flora can alter energy balance which can influence obesity. Another report suggests the possible role of some unknown virus (obesigenic virus) to cause obesity.

Genetic Syndromes (rare) associated with Obesity:

The “ob” gene is responsible for thinness, which produces leptin (the word is derived from the Greek root leptos, meaning thin), high level of which is responsible for reduced food intake and increase energy expenditure. Leptin is secreted by secreted by adipose tissues (fat cells) and act through hypothalamus. Mutation in “ob” gene in mouse causes severe obesity (due to presence of efficient metabolism in them i.e. they store fat even when intake of food calories is same as lean fellow mousses), insulin resistance, and excessive eating.

The “OB” gene is present in humans also and present in fat cells. Some families have morbid, early-onset obesity (soon after birth) and have neuroendocrine abnormalities and are caused by mutations which inactivate leptin or the leptin receptor. The hypogonadotropic hypogonadism is the most prominent feature of these families, which is reversed by leptin replacement. Fortunately this is a rare condition.

Mutations in genes can cause obesity (severe) in humans. These are listed below:

• Lep (ob) gene: this gene produce leptin and mutation of this gene prevents leptin from delivering satiety signal which perceives as brain starvation and the individual eat excess food.
• LepR (db) gene: this gene produce leptin receptor and mutation of this gene prevents leptin from delivering satiety signal which perceives as brain starvation.
• POMC gene: this gene produces proopiomelanocortin, a precursor of several hormones and neuropeptides. Mutation of this gene prevents synthesis of MSH (melanocyte-stimulating hormone), a satiety signal to brain.
• PC-1 gene: this gene produce prohormone convertase 1, a processing enzyme and mutation of this gene prevents synthesis of neuropeptide, including MSH.
• Fat gene: this gene produce a processing enzyme carboxypeptidase E, mutation of this gene prevents synthesis of neuropeptide, including MSH.
• MC4R gene: this gene produce type-4 receptor for MSH and mutation of this gene prevents reception of satiety signal from MSH.
• AgRP gene: this gene produces agouti-related peptide, a neuropeptide expressed in the hypothalamus mutation of this gene cause overexpression, which inhibits signal through MC4R.
• Tub gene: tub is a protein in hypothalamus and mutation of this gene cause hypothalamic dysfunction.
• TrkB gene: this gene produces TrkB, a neurotrophin receptor and mutation of this gene excessive hunger and eating due to defect in hypothalamus.