Weizmann team finds one brain gene keeps stress and metabolism in balance

Scientists at the Weizmann Institute of Science in Israel reported on 17 August 2026 that a gene long thought to matter mainly for building the embryonic brain keeps working throughout adult life as a control hub for stress and metabolism. The study, published in the journal Endocrinology, was led by Prof. Gil Levkowitz and Prof. Alon Chen with staff scientist Dr. Yael Kuperman and colleagues, including Dr. Jakob Biran of Israel's Volcani Institute.

The gene, called Orthopedia or Otp, helps form the hypothalamus, the small brain region that runs the body's hormone systems. Mice born without it die in infancy, so its role in adults had never been tested. The team used genetic tools and a drug to switch the gene off only after the animals' brains had fully developed.

The effects reached across body and behaviour. The mice produced more of the stress hormone corticosterone, coped poorly with stress and showed depression-like behaviour, giving up quickly in a swimming test. Their thyroid hormone levels dropped, their body temperature fell and their cholesterol and blood sugar rose. Although they ate normally and kept a normal weight, they carried more body fat and responded less to hunger signals. In the hypothalamus, Otp turned out to drive a hunger-promoting peptide called AgRP while also influencing cells that control energy use, suggesting it balances opposing circuits.

Levkowitz said the gene does not only build the system but keeps it running. The researchers argue that stress and metabolic disorders may share a common regulator, and that some cases could trace back to development while others arise from a breakdown later in life. Because Otp acts on several branches of the hormonal network, future treatments might target a single branch rather than the whole system. Prof. Danny Ben-Zvi of the Hebrew University, who was not involved, told The Times of Israel the work could help people with anxiety and metabolic disorders. The study used only male mice, and human applications remain speculative.