Why does dieting not work? Study sheds light

Many of us know from experience that losing weight is a feat of endurance. Some diets will work, others won't, and despite our best efforts, it might seem at times as though a diet makes us put on even more weight. So why does dieting not work? A new study finds a mechanism that may explain how our body limits weight loss, working against us when we are trying to lose weight.

New research helps to explain why sometimes, diets simply do not allow us to lose weight.

New research published in the journal eLife has uncovered a mechanism in mice that may be responsible for those frustrating moments in a dieter's life when nothing seems to work.

Mice, our fellow mammals, share enough similarities with the human body to provide a good model for understanding how our body responds to weight loss efforts.

The team of researchers - led by Dr. Clemence Blouet from the Metabolic Research Laboratories at the University of Cambridge in the United Kingdom - examined a group of neurons in the brain's hypothalamus and their role in regulating appetite.

The hypothalamus is a brain area responsible for producing hormones that regulate a series of bodily functions, ranging from body temperature and hunger, to mood, libido, and sleep.

This brain region contains a group of neurons called "agouti-related neuropeptides" (AGRP), which play a key role in regulating appetite. When AGRP neurons are "on," we want to eat, but when these neurons are deactivated, they can make us stop eating almost completely. AGRP neurons have the same effect in animals.

Testing the effect of AGRP neurons in mice

Dr. Blouet and team used genetics to switch these neurons "on" and "off" in mice. They used transgenic mice that had been modified to have the hM3Dq designer receptor, which can only be activated by designer drugs.

This genetic "shortcut" was tested in previous studies, which used evolved G protein-coupled receptors to control the neural activity in mice remotely.

The mice were examined in special "metabolic chambers" that can measure energy expenditure. They were also fitted with probes that measured their body temperature - which is also an indicator of how much energy the body is expending.

Dr. Blouet and colleagues took energy expenditure measurements in different situations - namely, in situations where food was either more or less available.

The experiments revealed that "artificially activating the neurons in mice that don't have access to food increases the animals' activity levels but reduces the rate at which they burn calories."

This helps the mice to maintain the same weight. However, when the small rodents were allowed to eat - or even just smell or see the food - their energy expenditure levels went back to normal.

"Finally, exposing mice to a high-fat diet for several days inhibits their AGRP neurons, and causes the animals to burn calories at a faster rate," report the authors.

In other words, AGRP neurons regulate our appetite depending on the amount of food that is available.

The study's lead investigator explains further:

"Weight loss strategies are often inefficient because the body works like a thermostat and couples the amount of calories we burn to the amount of calories we eat. When we eat less, our body compensates and burns fewer calories, which makes losing weight harder.

Our findings suggest that a group of neurons in the brain coordinate appetite and energy expenditure, and can turn a switch on and off to burn or spare calories depending on what's available in the environment. If food is available, they make us eat, and if food is scarce, they turn our body into saving mode and stop us from burning fat."

Dr. Blouet goes on to speculate that from an evolutionary perspective, such a mechanism may have evolved in order to help animals cope with famine. Evidently, in the case of dieting, the brain cannot tell that the person is intentionally trying to lose weight.

The study's first author, Dr. Luke Burke, also explains what these findings mean to the person who is trying to lose weight:

"This study could help in the design of new or improved therapies in future to help reduce overeating and obesity. Until then, [the] best solution for people to lose weight - at least for those who are only moderately overweight - is a combination of exercise and a moderate reduction in caloric intake."

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Weight Loss