One Gene May Be Quietly Impacting Your Ability To Lose Weight in Adulthood

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Key points

• Researchers at the Weizmann Institute of Science in Israel discovered that the gene, called Orthopedia, or Otp, does not switch off once the brain finishes developing.
• She continued: Orthopedia is a transcription factor that is essential to embryonic development, and is primarily identified in the hypothalamus.
• 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?
• Mice without functioning Otp published excess stress hormones, including corticosterone, and demonstrated signs of depression-like behavior, withdrawing from challenges and giving up more easily.
• Disruption of the developmental factor Otp in the adult male forebrain reveals its diverse physiological functions.

Meanwhile, 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 discovered 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 feasible explanation for why stress and weight gain so often go hand in hand. Transcription factors are special proteins that essentially support turn genes on or off. These proteins are what support differentiate cells from each other, and assist 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, informed Newsweek. She continued: Orthopedia is a transcription factor that is essential to embryonic development, and is primarily identified in the hypothalamus. It 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 extra responsibility. Newsweek reached out to the study authors for more information via email. A Gene That Never Clocks Out 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, indicated 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 published excess stress hormones, including corticosterone, and demonstrated signs of depression-like behavior, withdrawing from challenges and giving up more easily. Their metabolism additionally faltered: thyroid hormone levels dropped, body temperature fell and cholesterol rose. Although the mice ate normally and weighed the same as unaltered mice, they stored more body fat and responded more weakly to hunger signals. Researchers describe Otp as functioning like a switchboard operator, picking up incoming signals from inside the body and from the environment, then routing them to the DNA that decides which hormonal systems switch on. For context, the findings suggest evolution repurposed the same genetic machinery for two particularly different tasks. During development, Otp helps brain cells specialize. In adulthood, that same system gets redirected to manage daily stress and energy employ, sometimes triggering opposing effects, such as promoting hunger while additionally encouraging the body to burn energy, so as to keep the system balanced. We found that the same genetic program that shapes the brain's wiring during embryonic development continues to play a central role in regulating the organism's stress response and energy balance throughout its lifetime, Levkowitz remarked in an official note. We have identified a new master regulator of balance in the brain and body. Understanding in greater detail how it works may one day lead to more precise ways of treating different aspects of stress and metabolic dysfunction-not by shutting the system down when something is not working properly, but by nudging it back into balance. McCarthy added: The findings suggested that Otp isn't just a developmental transcription factor, instead, it appears to remain an active regulator of adult hypothalamic function, helping coordinate the brain's responses to stress, thyroid signaling, temperature, body composition, and hunger-related signals, notably regulating the adult stress response system. The psychologist continued that the study does a good job of highlighting just how interconnected our regulatory systems are. What we observe externally as a single 'behavior' may actually be the endpoint of a much larger brain-body calculation, she remarked. This is why I stress with my patients the importance of having a physical every year, and blood work at least once a year, or perhaps more, to identify or rule out any physiological issues that may be impacting real-time behavior. Reference Levkowitz, G., Chen A., et al. (2026). Disruption of the developmental factor Otp in the adult male forebrain reveals its diverse physiological functions. Endocrinology. Contact Newsweek editors on this story: Sirena Bergman and Cristina Diciu.

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Researchers at the Weizmann Institute of Science in Israel discovered 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 feasible explanation for why stress and weight gain so often go hand in hand.

"Transcription factors are special proteins that essentially support turn genes on or off. These proteins are what support differentiate cells from each other, and assist 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, informed Newsweek.

She continued: Orthopedia is a transcription factor that is essential to embryonic development, and is primarily identified in the hypothalamus. It 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 extra responsibility."

Newsweek reached out to the study authors for more information via email. A Gene That Never Clocks Out.

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, indicated 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.

For context, the results were striking. Mice without functioning Otp published excess stress hormones, including corticosterone, and demonstrated signs of depression-like behavior, withdrawing from challenges and giving up more easily. Their metabolism additionally faltered: thyroid hormone levels dropped, body temperature fell and cholesterol rose. Although the mice ate normally and weighed the same as unaltered mice, they stored more body fat and responded more weakly to hunger signals.

Researchers describe Otp as functioning like a switchboard operator, picking up incoming signals from inside the body and from the environment, then routing them to the DNA that decides which hormonal systems switch on.

For context, the findings suggest evolution repurposed the same genetic machinery for two particularly different tasks.

During development, Otp helps brain cells specialize. In adulthood, that same system gets redirected to manage daily stress and energy employ, sometimes triggering opposing effects, such as promoting hunger while additionally encouraging the body to burn energy, so as to keep the system balanced.

"We found that the same genetic program that shapes the brain's wiring during embryonic development continues to play a central role in regulating the organism's stress response and energy balance throughout its lifetime, " Levkowitz remarked in an official note. "We have identified a new master regulator of balance in the brain and body. Understanding in greater detail how it works may one day lead to more precise ways of treating different aspects of stress and metabolic dysfunction-not by shutting the system down when something is not working properly, but by nudging it back into balance."

McCarthy continued: "The findings suggested that Otp isn't just a developmental transcription factor, instead, it appears to remain an active regulator of adult hypothalamic function, helping coordinate the brain's responses to stress, thyroid signaling, temperature, body composition, and hunger-related signals, notably regulating the adult stress response system."

In practice, the psychologist continued that the study does a good job of highlighting just how interconnected our regulatory systems are.

"What we observe externally as a single 'behavior' may actually be the endpoint of a much larger brain-body calculation, " she remarked. "This is why I stress with my patients the importance of having a physical every year, and blood work at least once a year, or perhaps more, to identify or rule out any physiological issues that may be impacting real-time behavior."

Levkowitz, G., Chen A., et al. (2026). Disruption of the developmental factor Otp in the adult male forebrain reveals its diverse physiological functions. Endocrinology. Contact Newsweek editors on this story: Sirena Bergman and Cristina Diciu.

Taken together, the developments around one Gene May Be Quietly Impacting Your Ability To Lose Weight in point to a situation that is still moving, and the coming days should bring more clarity.