Impaired Brain Switch May Cause Obesity: Study Reveals

Highlights

• A mechanism by which the brain coordinates feeding with energy expenditure has been identified.
• The brain's ability to sense insulin after glucose breakdown and coordinate feeding is controlled by a switch-like mechanism.
• In cases of obesity, browning is turned off all the time and energy expenditure is decreased, leading to weight gain.

Obesity or excessive weight gain occurs due to various reasons but one of the simple reasons is when there is an imbalance between energy intake and expenditure. "Obesity is a major and leading factor in overall disease burden worldwide and is poised, for the first time in modern history, to lead to falls in overall life expectancy," Professor Tiganis said.

Fat in the human body is stored in specialized cells called adipocytes. Depending on the energy needs, adipocytes can change from white to brown states and back again.

Researchers from the Metabolic Disease and Obesity Program have shown in laboratory models that feeding controls the 'browning' of fat, that is, the conversion of white fat, which stores energy, into brown fat, which expends it.

Brown Fat Facilitates Energy Expenditure

Their study, published in Cell Metabolism, shows that after a meal the brain responds to circulating insulin, which is increased after a rise in blood glucose. The brain then sends signals to promote the browning of fat to expend energy.

After a fast, the brain instructs the browned adipocytes to be converted into white adipocytes, to store energy. By this process, excess weight gain or weight loss is prevented in response to feeding and fasting, meaning body weight remains relatively stable over time.

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Switch-Like Mechanism

The research team showed that a switch-like mechanism co-ordinates with the brain's signals in response to hunger and feeding. After the breakdown of food, the brain releases insulin and coordinates feeding with energy expenditure via browning. During a period of fast, the brain inhibits the response to insulin, repressing browning and conserving energy, and facilitates the insulin response to promote browning and to expend energy.

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"What happens in the context of obesity is that the switch stays on all the time - it doesn't turn on off during feeding," lead researcher Professor Tony Tiganis said.

"As a consequence, browning is turned off all the time and energy expenditure is decreased all the time, so when you eat, you don't see a commensurate increase in energy expenditure - and that promotes weight gain," Professor Tiganis said.

Previous investigations by the researchers that showed how the brain coordinates white adipose tissue browning attracted considerable attention after it was published in early 2015. The researchers are further exploring the possibility of inhibiting the switch for therapeutic purposes to promote the shedding of excess fat.

"What our studies have shown is that there is a fundamental mechanism at play that normally ensures that energy expenditure is matched with energy intake. When this is defective, you put on more weight. Potentially we may be able to rewire this mechanism to promote energy expenditure and weight loss in obese individuals. But any potential therapy is a long way off," he said.

Reference

1. Garron Dodd et al., Revealed: brain 'switch' tells body to burn fat after a meal, Cell Metabolism (2017).

Source-Medindia