Weizmann Scientists Identify Gene Controlling Stress Response, Metabolism, and Mood
Researchers at the Weizmann Institute of Science have uncovered a key biological mechanism linking mental stress responses with energy balance and metabolism. Their study, published in Endocrinology, reveals that the gene Otp, previously known for shaping brain development in the womb, remains active throughout adulthood. Otp regulates vital hormonal systems that influence stress reactions, metabolic rate, and behavior.
The team, led by Prof. Gil Levkowitz in collaboration with Prof. Alon Chen's group, demonstrated that disabling Otp in specific hypothalamic cells of adult mice caused overactivation of stress systems, elevated corticosterone hormone levels, depression-like behaviors, and reduced mental resilience. Metabolic disruptions included lower thyroid hormone levels, decreased body temperature, increased cholesterol, and higher body fat despite unchanged food intake and weight.
This gene acts as a master switch coordinating hormonal signals affecting both stress and metabolism. The findings suggest that mental health disorders like depression and anxiety may sometimes stem from hormonal imbalances involving thyroid hormones, which also impact cholesterol, blood sugar, and overall metabolism. Evolutionarily, Otp repurposes developmental brain wiring mechanisms to maintain energy and stress balance in adulthood.
The researchers used advanced genetic tools to selectively inhibit Otp in adult mice without affecting brain development, highlighting its ongoing regulatory role. They propose that understanding Otp's function could lead to targeted treatments for conditions ranging from mood disorders to diabetes by restoring hormonal and metabolic equilibrium rather than shutting down entire systems.
The study involved collaboration among the Weizmann Institute's Molecular Cell Biology, Neuroscience, and Molecular Neurobiology departments, with contributions from scientists including Dr. Yael Cooperman, Maayan Tahor, and others from the Volcani Institute.
