“I can’t help being fat, it’s in my genes!’ We hear this statement quite often but is it the whole truth?  Obesity is a major global health problem. In 2005, it was estimated that at least 400 million adults were obese (BMI > 30) world-wide. By 2015, it is estimated that the number will increase to about 700 million. Genome-wide studies have identified 12 alleles (an allele is a locus on a chromosome where the DNA is different) that are associated with increased BMI. Does the possession of one or more of these alleles sentence you to a life of obesity? Or could you influence this genetic predisposition to increased obesity risk by lifestyle changes?

Researchers from Cambridge University genotyped the 12 loci in a population-based sample of 20,430 adults from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort and assessed the influence of a physically active lifestyle on the genetic predisposition to obesity in these individuals (PLoS Med 7(8): e1000332. doi:10.1371/journal.pmed.1000332). The study showed that, in a 1.70 metre tall person, every additional BMI-increasing allele was associated with an increase in BMI equivalent to 445 gm in body weight. In physically inactive individuals, the increase was 592 gm per allele. In physically active individuals, the increase was 36% lower at 379 gm per allele. In physically inactive individuals, possession of one of these obesity-susceptibility alleles increases the obesity risk by 15.8%. However, in physically active individuals the risk is 40% less at 9.5%.

While possession of the wrong genes can predispose an individual to weight gain, the trigger for weight gain is not purely genetic. We have to provide that trigger in the form of inappropriate lifestyle choices. Eating more than we need, eating foods that are high in fat and sugars, lack of physical activity due to increasingly sedentary lifestyles are all triggers to the worldwide obesity epidemic. Becoming obese not only affects self esteem and image, it also brings with it a slew of health problems such as heart disease, hypertension, diabetes, steatohepatitis, joint problems and cancer.

The next time you are about to blame your weight gain on mother nature, perhaps you might want to think again!

On Sunday, 14^th December, Reuters carried the news that researchers from the National Human Genome Research Institute and deCode Genetics Inc. of Iceland had found six new gene mutations linked to obesity. [deCode Genetics (DCGN) is a listed company on the NASDAQ stock exchange.]

A gene is made up of a sequence of 4 different nucleotides which code for amino acids. The researchers analysed 300,000 one-letter (= one nucleotide) mutations in the genetic code in more than 30,000 people from Iceland, the Netherlands and the United States. (One-letter mutations in the genetic code are called single nucleotide polymorphisms or SNPs.)  They cross-checked their findings in 40,000 people from Denmark and the United States and found variations in 6 genes – TMEM 18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 – which were strongly associated with body mass index (BMI).

One of the researchers from the National Human Genome Research Institute was excited by these findings as they could be a major step forward in understanding how the human body regulates weight. The CEO of deCode Genetics, however, was more excited at the prospect of using these discoveries as the first step in developing new drugs and by the fact that these new SNPs may point to valuable new drug targets.

Thirty to forty years ago, global obesity was not a major health issue. The last I checked, the human race has not made a major evolutionary change, suddenly making mankind obese an evolutionary advantage. What has changed in the last 3 – 4 decades is our lifestyle and eating habits. We have become more dependent on vehicles to get us from point A to point B. We want to be entertained by sitting in front of the TV or computer screen. We have taken to eating a bigger portion of food and also eating more junk food. We are tempted by the ‘up size’ offer when we order our food. We certainly have shunned physical activities and outdoor pursuits.

I am sure these SNPs linked to high BMI did not appear overnight. For all we know they could have been in the population before. Perhaps, over the last several decades, what we eat and what we do somehow triggered the SNPs to alter our body regulation of appetite or metabolism. Instead of waiting for a pharmaceutical company to come up with a new pill for obesity, would it not be more logical to watch what we eat and to exercise regularly in order to stave off the ever rising BMI? I for one would not be in favour of reaching for the pill!