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Scientists re-create brain neurons to study obesity
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Researchers from Cedars-Sinai have developed a new way to study the brain’s role in obesity, which involves re-creating the brain neurons of adults with the disease, according to a press release from the institution.
The study focuses primarily on the hypothalamus — the region of the brain that regulates hunger and satiety — and the ways in which neurons interact and aid in communication between the brain and gastrointestinal tract, according to the release.
“Understanding how this signaling process works at the cellular level is important in providing much-needed clues for future treatment strategies for obesity,” Dhruv Sareen, PhD, assistant professor of biomedical sciences at Cedars-Sinai and director of the Induced Pluripotent Stem Cell Core Facility at the Cedars-Sinai Board of Governors Regenerative Medicine Institute, said in the release. “But the process is difficult to investigate because hypothalamus tissues from living patients are not readily accessible for direct examination.”
Through their use of stem-cell technology, the researchers were able to reproduce hypothalamic neurons outside the body. The researchers genetically reprogrammed blood and skin cells from five adults with super-obesity (BMI at least 50 kg/m2) and seven adults defined as having a normal weight (BMI less than 25 kg/m2). The neurons mirrored the genetics of the patients who donated the original cells.
Researchers found that the neurons of adults with super-obesity contained multiple genetic mutations and responded abnormally to hormones that regulate hunger, satiety and metabolism.
“We were pleasantly surprised that reprogramming patient-derived adult cells into an induced pluripotent stem cell state, and then re-differentiating them to form hypothalamic neurons, revealed brain-specific disease phenotypes and molecular profiles that are known to exist in obesity,” Sareen explained to Endocrine Today.
“The ultimate goal is to identify early biomarkers of obesity and other metabolic diseases and accelerate therapeutic interventions in patients with these diseases. We are also paving the way for precision medicine, in which drugs could be customized for individual obese patients with different genetic backgrounds and disease status,” Sareen said. – by Melissa J. Webb
Disclosure: The study was funded by Cedars-Sinai and the National Center for Advancing Translational Science of the National Institutes of Health. The authors report no other relevant financial disclosures.