In two separate papers, published in the journal Science and in the Journal of Clinical Investigation (JCI), researchers describe new genetic factors that could explain weight gain in some people.

In the Science study, researchers at Boston Children’s Hospital studying mice found a rare genetic mutation that prevented the animals from burning off fat kilojoules. They also found the same gene was mutated in a group of obese people. And a team based at University College London reported in JCI that a specific form of a gene previously linked to obesity, FTO, can increase craving for high-fat foods.

The biology behind weight

The discoveries add to the growing body of knowledge about the biology behind weight, and the results confirm that while it’s represented by a single number, weight is the complex combination of a multitude of different metabolic processes, from brain systems that regulate appetite to enzymes that control how efficiently kilojoules are turned from food into energy that the body needs. Making matters even more confusing, these factors are also likely influenced by environmental contributors such as diet and lifestyle.

Mutant genes

“Thus far mutations in about eight genes are known to cause obesity in humans. But these mutations account for under five percent of the obesity in our society, and certainly are not, by themselves, responsible for the current obesity epidemic, since the mutation rate in these genes could not have changed dramatically during the past 20 years,” says Dr Joseph Majzoub, the chief of the division of endocrinology at Boston Children’s Hospital and an author on the Science paper.

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“However, mutations in these genes have led to the discovery of pathways that are important in energy balance in humans, giving us hope that drugs can be developed that affect these pathways to prevent excessive weight gain, either by curbing appetite or increased burning of kilojoules.”

Three genes linked to obesity

Leptin: Often referred to as the “obesity hormone,” leptin is made by fat cells and acts as a thermostat for the body’s energy needs. Each individual has his own leptin threshold; if leptin levels fall below that amount, the brain understands that the body is starving, and needs more kilojoules. If leptin levels are maintained or surge above that amount, the brain knows that it doesn’t need to take in more food.

Unfortunately, while mouse studies showed that overweight mice had lower levels of leptin, the same wasn’t true of obese people, who generally show higher levels of leptin in their blood. Somehow, researchers believe, these people are not getting the signal to stop eating, which is referred to as leptin-resistance.

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Ghrelin: This gene makes an appetite hormone that can make foods look more desirable – especially high-kilojoule ones – by influencing the brain’s reward system. Some studies have found that people who are sleep-deprived have increased ghrelin levels, which may explain why lack of sleep can contribute to weight gain.

Neuropeptide Y: One of the brain’s many chemicals, neuropeptide Y may trigger eating by manipulating appetite, possibly resulting from changes in mood and stress levels. It may also contribute to an increased deposition of fat from food kilojoules.