Why is NZ getting so FAT?
Eat sugar and fat, get fat. Conventional wisdom tells us that’s all there is to obesity. The bad news is it’s not that simple. Even worse, there is still too much we don’t know. Jamie Morton explains.
There was a time, says Professor Peter Shepherd, when our best hope against cancer was the catchall approach of chemotherapy. Revolutionary advances in the field have since delivered us into a new age of individualised drugs and interventions.
Yet, the renowned Auckland University scientist worries, our grasp of the tangle of complex drivers underlying obesity — an epidemic overtaking even smoking as a health burden — lags where cancer research was mired all those decades ago.
“In many ways, we are in the dark ages of our understanding metabolic diseases,” Shepherd says. “Only now are we starting to learn that it really does involve a whole range of different causes, in a whole range of different individuals.”
Shepherd says the simple problem is an environment problem — fatty, sugar-heavy diets creating an energy overload we can’t burn off — and one worsened under today’s onslaught of junk food exposure. But the tougher problem is working out why some are more at risk than others.
That means not only understanding the tens of thousands of genes in our genetic jigsaw — but also how those genes interact and change with the environment we put them in.
“If we’ve all got combination locks that have 20 different numbers; it’s quite complicated getting them all to line up to unlock the obesity puzzle,” says Professor Wayne Cutfield, a paediatric endocrinologist at Auckland University’s Liggins Institute.
“Things like diet, medication, activity can all change the way that genes behave, and it’s becoming increasingly clear epigenetics — or the way in which genes are turned on and off by environment — are coming into play.”
THE GENETIC PUZZLE
It is frontier science, but researchers have suspected for half a century that genes have a hidden role.
Back in 1962, geneticist James Neel proposed humans once had “thrifty genes” that doled out energy intake to our prehistoric hunter-gatherer ancestors over times of famine and feast, and their unsuitability to today’s world of plenty exacerbated obesity.
There is evidence to suggest this effect may play out in some populations today — among them Pima Indians and Pacific Islanders — but scientists today don’t ever expect to find Neel’s universal, enigmatic thrifty gene.
Criticism of that evolutionary argument actually led to a new path of thinking: we can’t look at genes in isolation and what’s really evolving is our own organism, tightly in step with our environment.
Shepherd believes half of obesity might be explained by a wide range of genes contributing to overall risk.
“For most people, it’s those different genes regulating your propensity to eat, your ability to metabolise the food that you do take in, whether you absorb it from your gut in the first place, or whether you store it in your fatty cells or elsewhere.”
This appreciation grew in the 1990s, with discoveries that pinpointed multiple genes directly affecting appetite and metabolism.
Then DNA technology let us sequence, or download, the human genome for the first time, meaning scientists could delve much deeper into our genetic make-up.
More than 50 different genes have since been reported as being related to obesity phenotypes, yet just 10 have so far been conclusively linked.
But answers could lie outside those regions of
DNA that have codes that create proteins in cells
— in areas we call “junk DNA”.
Just last year, Liggins researchers found genetic changes hidden in these supposedly useless areas, uncovering a possible missing link between type 2 diabetes and obesity. The fact obesity and diabetes so often affect the same people has led scientists to suspect similar genes are contributing to the development of the disorders.
“Every day, we are making new findings — and what’s clear is each individual in our world has a different subset of genes and gene variants, which means we are all at different risks for all sorts of diseases,” Shepherd says.
“But, in the case of obesity, if we are all put in the same environment, we will all respond differently.”
Scientists imagine an age of individualised healthcare, much like for cancer treatment, where obesity interventions won’t just be based on nutrition, but also on genetic predisposition.
To get there, says Associate Professor Justin O’Sullivan, another leading Liggins researcher, we need to boil down the populationscale picture to the personal.
It’s the big aim of the GENO Project, a new transtasman effort tapping into a longitudinal study of 10,000 Australian children and nearly 2000 parent-child pairs, making it one of the richest such datasets in the world.
The effort will be helped by a seminal discovery O’Sullivan helped make in 2014.
It revealed how a microscopic, effortlessly efficient organisational structure inside DNA was involved in turning genes on and off — something that could distinguish each of the 200 different cell types in our bodies and weed out new insights from the GENO data.
Understanding the way DNA “folded” to reveal tissues affected by genetic variation, he says, might ultimately mean scientists can predict the risk of developing certain non-communicable diseases later on in life.
But already, a third of Kiwi kids are considered either obese or overweight — disproportionately among Māori and Pacific Island children — and rates are rising fast.
A HEAD-START
More troubling is the building evidence that children could be at risk of obesity before they are even conceived.
“We now know that a mother’s weight before conception is almost as important as how much weight she gains during pregnancy,” Cutfield says.
“So the mother’s diet and activity just prior to conception is crucial.”
As is the health of the father.
Obesity can regulate the way in which genes in sperm behave, raising the risk in the child — a theory that wasn’t demonstrated until 2015.
“We are beginning to appreciate that the father is increasingly important, and we are still trying to understand exactly what it is in the pre-conceptual phase that is important for the mother,” Cutfield says.
Pregnancy itself is where much of the Liggins Institute’s focus lies and is a big reason it’s regarded as a world leader.
Thanks to its research, we know premature birth can raise the risk of obesity, and that first-borns have greater difficulty absorbing sugars into the body, among other landmark findings.
Fascinating current studies include an investigation into whether artificial sweeteners are as bad for pregnant women as regular sugary drinks, and whether fish oil supplements taken in pregnancy can help combat weight problems in children down the track. Again, there’s a long way to go. “A healthy diet is promoted in pregnancy, but what an optimal diet actually is, we still haven’t got that totally sorted,” Cutfield says.
OUR ARMY OF BUGS
Another focus is the microbiome — essentially an army of microbes that keeps us alive by breaking down food to release energy, protecting us from germs and producing vitamins.
“You can think about our whole human genome as two parts: we have the fixed part, which is basically ours,” says O’Sullivan.
“And then you’ve got the plastic part, which is modified by the environment and everything else — that’s the microbiome.”
When we eat, rapidly digested food is absorbed in our small intestine and distributed straight into the system as energy.
But if the food gets all the way to our large intestine, our microbes can play a much bigger role.
Some of those bacterial processes have good effects on our body — and some don’t.
Studies have turned up correlations between obesity and the microbiome but O’Sullivan adds that is not the same as cause-and-effect.
“The short answer: it seems to contribute and associate with obesity, but how that works we are not sure.”
Some promising research has suggested it’s possible to target the microbiome with specific drugs — or even import an entire healthy microbiome through what have