A single gene known for shaping the brain before birth appears to keep working long after childhood, quietly steering how the body handles stress and stores fat, according to a new study. Researchers at the Weizmann Institute of Science in Israel found that the gene, called Orthopedia, or Otp, does not switch off once the brain finishes developing. Instead, it stays active into adulthood, helping control the hormonal systems that govern stress responses, metabolism and behavior.
The discovery, published in Endocrinology, offers a possible explanation for why stress and weight gain so often go hand in hand. "Transcription factors are special proteins that essentially help turn genes on or off. These proteins are what help differentiate cells from each other, and help cells grow over time and react to environmental changes external to the cell, such as shifts in temperature or hormone fluctuations," Dr.
Jessica McCarthy, a licensed clinical psychologist, told Newsweek. She added: "Orthopedia is a transcription factor that is essential to embryonic development, and is primarily found in the hypothalamus, which is responsible for the regulation of neuroendocrine systems, stress, and metabolic balance. "The absence of Otp, especially during the embryonic stage, is lethal.
The researchers were curious to see if Otp had any additional responsibility." Newsweek reached out to the study authors for more information via email. Otp works inside the cell nucleus and is essential for survival. The gene has long been studied for its role in building the hypothalamus, the brain region that manages basic survival functions like hunger, sleep, reproduction and stress.
More than a decade ago, the same research team, led by Professor Gil Levkowitz in collaboration with Professor Alon Chen, showed that disrupting Otp during early brain development in zebrafish left the fish unable to mount a normal stress response as adults. That raised a question researchers could not yet answer: was Otp still doing something in the adult brain, or was its job finished at birth? To find out, the team turned to mice and built a genetic tool that let them switch off Otp in specific brain cells in adults only, leaving earlier brain development untouched.
The results were striking. Mice without functioning Otp released excess stress hormones, including corticosterone, and showed signs of depression-like behavior, withdrawing from challenges and giving up more easily. Their metabolism also faltered: thyroid hormone levels dropped, body temperature fell and cholesterol rose.
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