Does Circadian Misalignment Have Sex-Specific Effects on Metabolism?

This study will examine whether biological sex affects how the body responds to circadian misalignment-a mismatch between a person's internal body clock and their sleep/wake and eating schedule (similar to what can happen with night shift work, jet lag, or frequently changing sleep schedules). Researchers will measure how circadian misalignment influences appetite regulation (such as hunger and fullness) and glucose metabolism (how the body controls blood sugar), and whether these effects differ between females and males.

By identifying sex-specific responses to circadian misalignment, this research may help guide the development of safer, more personalized shift work schedules and targeted strategies to reduce metabolic health risks, with the goal of improving clinical care and reducing sex-related differences in metabolic disease risk.

• Day shift (Behavioral): Research participants will be assigned to day shift condition in which sleep-wake and meal schedules are aligned with the internal circadian system
• Night shift (Behavioral): Research participants will be assigned to simulated night shift condition in which sleep-wake and meal schedules are misaligned with the internal circadian system

Primary outcomes

• Difference in circulating leptin levels between Night Shift and Day Shift [24 hours]: Differences of 24-h circulating leptin levels on the test days in the two experimental conditions
• Differences in Disposition index (DI) derived from identical test breakfast between Night Shift and Day Shift [3 hours]: Disposition index (DI) derived from oral minimal model based on postprandial glucose, insulin, and c-peptide responses to identical test breakfast on the test days between protocols
• Differences in self-rated cravings for hyperpalatable food during the wake period between Night Shift and Day Shift. [16 hours]: Differences in self-rated cravings for hyperpalatable food during the wake period on the test days between protocols.

Sex: All, ages: 18 Years to 40 Years, accepts healthy volunteers

Inclusion Criteria:

* 18-40 years of age
* Body Mass Index 18.5-24.9 kg/m2
* Non-smokers, no current tobacco or e-cigarette use
* Healthy with no acute or chronic medical and psychiatric disorders
* Sex assigned at birth consistent with reproductive anatomy at enrollment (per protocol definition)

Exclusion Criteria:

* History of drug or alcohol dependency
* History of psychiatric illness or disorder
* Pregnant
* No prior gender-affirming hormone therapy and no gonadectomy

• Jingyi Qian, PhD, Principal investigator, Brigham and Women's Hospital