A CALORIE is a calorie. Eat too many and spend too few, and you will become obese and sickly. This is the conventional wisdom. But increasingly, it looks too simplistic. All calories do not seem to be created equal, and the way the body processes the same calories may vary dramatically from one person to the next.
This is the intriguing suggestion from the latest research into metabolic syndrome, the nasty clique that includes high blood pressure, high blood sugar, unbalanced cholesterol and, of course, obesity. This uniquely modern scourge has swept across America, where obesity rates are notoriously high. But it is also doing damage from Mexico to South Africa and India, raising levels of disease and pushing up health costs.
Metabolic syndrome can still be blamed on eating too much and exercising too little. But it is crucial to understand why some foods are particularly harmful and why some people gain more weight than others. Thankfully, researchers are beginning to offer explanations in a series of recent papers.
One debate concerns the villainy of glucose, which is found in starches, and fructose, found in fruits, table sugar and, not surprisingly, high-fructose corn syrup. Diets with a high “glycaemic index”, raising glucose levels in the blood, seem to promote metabolic problems. David Ludwig of Boston Children’s Hospital has shown that those on a diet with a low glycaemic index experience metabolic changes that help them keep weight off, compared with those fed a low-fat diet. This challenges the notion that a calorie is a calorie. Others, however, blame fructose, which seems to promote obesity and insulin resistance. Now a study published in Nature Communications by Richard Johnson, of the University of Colorado, explains that glucose may do its harm, in part, through its conversion to fructose.
Dr Johnson and his colleagues administered a diet of water and glucose to three types of mice. One group acted as a control and two others lacked enzymes that help the body process fructose. The normal mice developed a fatty liver and became resistant to insulin. The others were protected. The body’s conversion of glucose to fructose, therefore, seems to help spur metabolic woes.
You are what you eat, maybe
Even more intriguing is the notion that the same diet may be treated differently by different people. Four recent papers explored this theme. In one, published in Science in July, Joseph Majzoub, also of Boston Children’s Hospital, deleted in mice a gene called Mrap2. Dr Majzoub and his colleagues showed that this helps to control appetite. Surprisingly, however, even when the mutant critters ate the same as normal mice, they still gained more weight. Why that is remains unclear, but it may be through Mrap2’s effect on another gene, called Mc4r, which is known to be involved in weight gain.
The second and third papers, published as a pair in Nature in August, looked at another way that different bodies metabolise the same diet. Both studies were overseen by Dusko Ehrlich of the National Institute of Agricultural Research in France. One examined bacteria in nearly 300 Danish participants and found those with more diverse microbiota in their gut showed fewer signs of metabolic syndrome, including obesity and insulin resistance. The other study put 49 overweight participants on a high-fibre diet. Those who began with fewer bacterial species saw an increase in bacterial diversity and an improvement in metabolic indicators. This was not the case for those who already had a diverse microbiome, even when fed the same diet.
Jeffrey Gordon, of Washington University in St Louis, says these two studies point to the importance of what he calls “job vacancies” in the microbiota of the obese. Fed the proper diet, a person with more vacancies may see the jobs filled by helpful bacteria. In the fourth paper, by Dr Gordon and recently published in Science, he explores this in mice. To control for the effects of genetics, Dr Gordon found four pairs of human twins, with one twin obese and the other lean. He collected their stool, then transferred the twins’ bacteria to sets of mice. Fed an identical diet, the mice with bacteria from an obese twin became obese, whereas mice with bacteria from a thin twin remained lean.
Dr Gordon then tested what would happen when mice with different bacteria were housed together—mouse droppings help to transfer bacteria. Bacteria from the lean mice made their way to the mice with the obese twin’s bacteria, preventing those mice from gaining weight and developing other metabolic abnormalities. But the phenomenon did not work in reverse, probably due to Dr Gordon’s theory on the microbiota’s job vacancies. Interestingly, the invasion did not occur, and obesity was not prevented, when the mice ate a diet high in fat and low in fruits and vegetables. The transfer of helpful bacteria therefore seems to depend on diet.
Dr Gordon hopes to be able to identify specific bacteria that might, eventually, be isolated and used as a treatment for obesity. For now, however, he and other researchers are exposing a complex interplay of factors.
One type of calorie may be metabolised differently than another. But the effect of a particular diet depends on a person’s genes and bacteria. And that person’s bacteria are determined in part by his diet. Metabolic syndrome, it seems, hinges on an intricate relationship between food, bacteria and genetics. Understand it, and researchers will illuminate one of modernity’s most common ailments.
With The Economists
