‘Obesity master switch’ for burning fat discovered
SCIENTISTS who analyzed the cell-level circuits surrounding the activity of the FTO gene – the one most strongly associated with obesity – have discovered a metabolic pathway that appears to exert overall control over whether our fat cells store or burn calories.
Researchers have discovered a cell circuit that controls whether fat cells burn or store fat, which is regulated by a master gene that differs among individuals.
The discovery – published in The New England Journal of Medicine – may lead to new approaches to prevent and even cure obesity, says the team, from Massachusetts Institute of Technology (MIT) in Cambridge, and Harvard Medical School in Boston, MA, United States (US). Obesity is one of today’s biggest challenges to global health.
It affects over 500 million people worldwide and contributes to type 2 diabetes, cancer, and cardiovascular disorders – all diseases that can lead to early death.
Also, while it may be a convenient way to fit lunch into a hectic work schedule, new research published in the Journal of Health Psychology suggests that eating while “on the go” could lead to weight gain and obesity in people who are dieting. Eating while walking around led to increased snack food intake among the participants of a subsequent taste test.
The study, conducted by researchers from the University of Surrey in the United Kingdom (UK), found that eating while walking could make dieters overeat later on in the day, triggering more overeating than other forms of distraction such as watching television (TV) or chatting with a friend.
Senior author Manolis Kellis, professor of computer science at MIT, says: “Obesity has traditionally been seen as the result of an imbalance between the amount of food we eat and how much we exercise, but this view ignores the contribution of genetics to each individual’s metabolism.”
Since its discovery in 2007, scientists have been trying to find out about the cell-level mechanisms that link the FTO gene and its surrounding region to obesity.
While a number of discoveries have been made – for example, some studies have suggested the FTO region is linked to brain circuits that control appetite or urge to exercise – none have yet explained how genetic differences in the region lead to obesity.
First author Melina Claussnitzer, an instructor in medicine at Harvard Medical School and a visiting professor at MIT, says their findings reveal that the FTO region acts on immature fat cells without involving the brain.
For their study, the team examined known gene control circuits from over 100 tissues and cell types. They discovered evidence of a major gene control switchboard in human adipocyte progenitor cells – immature cells that become fat cells.
The researchers say this evidence supports the idea that genetic differences among individuals control how their bodies store and burn fat.
To explore this idea further, the researchers studied genetic differences in adipocytes, or fat cells, from healthy Europeans carrying either the high-risk version of FTO or the non-risk version.
They found that the high-risk version of FTO activates a major gene control switch that, in turn, switches on two genes in another part of the genome: IRX3 and IRX5. In further experiments, they established that IRX3 and IRX5 control thermogenesis – a cell process for using energy stores to generate heat – in fat cells. They, therefore, established a link from FTO to the control of whether fat cells burn or store fat, without going via the brain.
Lead author of the second study, Prof. Jane Ogden. “This may be because walking is a powerful form of distraction which disrupts our ability to process the impact eating has on our hunger,” “Or it may be because walking, even just around a corridor, can be regarded as a form of exercise which justifies overeating later on as a form of reward.”
Previous research has suggested that distraction can have a significant impact on food intake, with studies indicating that watching TV while eating can both increase food intake while watching and lead to inaccurate evaluation of actual food intake, increasing the risk of subsequent overeating. Similar studies have also suggested that food environments and social interactions can provide forms of distraction that influence the amount of food eaten during a meal.
However, most of this research has focused on the impact of distraction on concurrent rather than future food intake, the study authors write. As a result, the authors opted to explore the impact on future food intake by using a fixed meal intake during a period of distraction for the study participants.
A total of 60 female students categorized as dieters or non-dieters. The participants were each randomly assigned to eat a cereal bar under one of three different conditions.
One group watched a five-minute clip of a TV program while eating, another group had to walk along a corridor while eating and the final group ate while sat with a friend and having a conversation.
After eating the cereal bar, the participants completed a brief questionnaire about it before being asked to take part in an unsupervised taste test. Separate bowls of chocolate, carrot sticks, chips and grapes were presented to the participants, who were instructed to rate the foods according to how much they liked them and asked to “eat as much as you like.”
Distraction could disrupt association between food and mealtimes The researchers recorded how much of the food the participants had consumed after they had left the room.
Dieters who ate their cereal bar while walking around went on to eat more snacks during the taste test. In particular, the researchers found that they ate around five times more chocolate than other participants.
The researchers write that this finding supports the idea that higher levels of dietary restraint could make individuals more susceptible to the effects of distraction. They acknowledge, however, that the taste test was very close in time to the distraction intervention.
The researchers suggest that further research is needed to assess whether walking can trigger overeating in the longer term.
Ogden explains why distraction might affect food intake: “Fullness is not only the result of brain and chemical reactions, but a perception that is influenced by learning, emotion and distraction. If we eat ‘on the go’ or in front of a computer, we will feel less full as our attention is diverted away from the meal and we don’t learn the association between food and mealtimes.”
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