Fighting obesity by attacking both food intake and energy burn

Obesity
Scientists at Rockefeller University and Princeton hope to inspire anti-obesity drugs that reduce hunger and boost the burning of calories simultaneously. (Creative Commons CC0)

Most weight-loss drugs on the market today, including Vivus’ Qsymia, work by altering pathways in the brain that regulate hunger. But body weight is governed both by the calories we take in and those we burn, so is it possible that attacking both processes would yield more effective weight loss?

Researchers at Rockefeller University in New York believe the answer to that question is “yes.” So they teamed up with Princeton University scientists and went searching for brain cells that regulate both calorie intake and energy expenditure. What they found could inspire the development of more effective weight-loss drugs, they believe.

The researchers zeroed in on a region of the brainstem called the dorsal raphe nucleus, which houses neurons known to be involved in controlling hunger. In mouse studies, they discovered that inhibiting the neurons not only reduces food intake, it also increases energy expenditure. They published their findings in the journal Cell.

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The researchers started by using an advanced 3D-imaging tool developed at Rockefeller University to observe the brains of mice exposed to heat. After observing activity in the neurons in the dorsal raphe nucleus, they tried turning the neurons on and off. They discovered that suppressing the neurons caused the animals’ brown fat—often referred to as the “healthy” fat—to burn more energy.

"Our new findings demonstrate that these neurons regulate energy balance by modulating both food intake and energy expenditure through partially overlapping circuit mechanisms," said Princeton researcher Alexander Nectow, Ph.D., in a statement.

RELATED: CRISPR controls obesity in mice by amplifying rather than editing genes

The newest generation of weight-loss drugs has been largely disappointing. Expectations for Qsymia were high after its 2012 approval. But, so far, it's pulling in only $41 million in annual sales despite aggressive marketing on the part of Vivus.

The search for new ways to combat obesity is largely focused on harnessing the power of brown fat. Scientists at American University in Washington, D.C., for example, are working on several such approaches, including using stem cells to grow brown fat and targeting a signaling pathway that causes unhealthy white fat to take on the energy-burning properties of brown fat.

And last year, a team at the University of California, San Francisco, described a technique they’re developing that involves using the gene editing system CRISPR to activate the activity of obesity-fighting genes.

The next step for the Rockefeller-Princeton team is to search for receptors in the fat-fighting dorsal raphe nucleus neurons that control both energy expenditure and food intake. They believe that could spark the development of new anti-obesity drugs that can target both processes.

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