Scientists have understood that just a small change to this gene – called Melanocortin 4 or the MC4 receptor – can lead to the condition, but until now what controls that it hasn’t been clear.
That’s despite years of work by drug companies to find molecules that might activate it, said study co-author Associate Professor Kathy Mountjoy, of the University of Auckland.
“In large part, they have failed because the drugs they have discovered that will regulate the MC4 receptor have had unwanted side effects.”
The new insights, led by Mountjoy’s colleague, Dr Chen Liu, at the University of Texas, may have cracked the puzzle.
The key: a newly discovered gene called orthopedia, or OTP.
It’s shown to control how the gene is expressed in the brain’s hypothalamus, where our appetite and energy storage are regulated.
Scientists had earlier identified OTP – along with several mutations linked to obesity – among genetic data held in the UK Biobank, but they still didn’t know what the gene was doing.
When analysed more closely in mice studies, it was revealed mice with the same mutation became obese – proving that OTP was effectively regulating the MC4 gene to drive obesity.
“The key point is that the OTP gene regulates the expression of the MC4 gene in the brain’s hypothalamus – and its disruption causes obesity in mice and humans,” said Mountjoy, who also provided New Zealand-sourced DNA for the study.
There aren’t yet drugs that target regulators like OTP – and Mountjoy expected the findings were likely to prompt new development in the area.
“It will be a challenge, but it offers a potential way of treating obesity in the general population.”
The study comes as a major review published this week has prompted a rethink about how doctors should diagnose obesity.
Its authors criticised the definition of obesity being tied to BMI, a measurement of height and weight, as opposed to more accurate measurements of a person’s fat, muscle and bone mass.
They suggested new guidelines – categorising obesity as either causing chronic disease or minimal health risk – which the University of Auckland’s Professor Sir Collin Tukuitonga said could help reduce stigma and improve care.
Jamie Morton is a specialist in science and environmental reporting. He joined the Herald in 2011 and writes about everything from conservation and climate change to natural hazards and new technology.
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