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Cedars-Sinai

Do I Look Fat in these Genes?

Scientists recreate brain neurons to study obesity and personalize treatment.

Adria Fruitos

As unappetizing as “disease in a dish” sounds, Cedars-Sinai scientists cooked up this new technology to examine the role of the brain in obesity. Their findings may help reduce the heavy burden on a nation in which more than a third of adults are severely overweight.

“We are paving the way for personalized medicine, in which drugs could be customized for obese patients with different genetic backgrounds and disease statuses,” says Dhruv Sareen, PhD, director of the David and Janet Polak Foundation Stem Cell Core Laboratory at the Board of Governors Regenerative Medicine Institute at Cedars-Sinai.

The new study focused on the hypothalamus, the area of the brain that regulates hunger, thirst, body temperature, and other functions requiring hormonal control. Hypothalamic neurons produce and respond to chemicals that influence metabolism and enable communication between the brain and gastrointestinal tract.

Decoding the cellular signaling process without being able to access living brain tissue has been a challenge in the past, notes Sareen, senior author of the research. His laboratory circumvented this barrier by using stem cell technology to reproduce the brain’s hypothalamic neurons outside the body.

The research team sampled blood and skin cells from people considered “super obese”—defined as having a body mass index (BMI) of 50 or more—and others with normal BMI of 25 or under. The investigators genetically reprogrammed these cells into hypothalamic neurons that matched the genetics of each individual cell donor.

The team found that the neurons from super-obese patients contained multiple genetic mutations and responded abnormally to a number of hormones that regulate hunger, satiety, and metabolism.

“Understanding how this signaling process works at the cellular level provides much-needed clues for future treatment strategies for obesity,” Sareen says.

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