In a new study from Kyushu University in Fukuoka, Japan, researchers have uncovered striking differences in how chronic jet lag affects the metabolism of male and female mice. The findings, published in the journal Biology of Sex Differences, reveal that while jet-lagged male mice gain weight and develop glucose intolerance, their female counterparts lose weight compared to those unaffected by jet lag. This discovery challenges the widely held assumption that jet lag universally leads to weight gain and underscores the role of sex hormones in shaping metabolic responses.
The research team, led by Professor Shinobu Yasuo from Kyushu University’s Faculty of Agriculture, subjected mice to conditions mimicking chronic jet lag by repeatedly shifting their light-dark cycles. For the control group, lights were switched on and off every 12 hours, maintaining a stable rhythm. In contrast, the jetlagged group experienced a six-hour forward shift every two days over eight weeks. The results were unexpected. “We expected both male and female mice to gain weight under chronic jet lag, just to varying degrees,” Professor Yasuo admitted. Instead, the metabolic outcomes diverged sharply between the sexes.
Male mice under chronic jet lag conditions packed on extra weight and showed signs of glucose intolerance, a precursor to diabetes. Meanwhile, female mice lost weight compared to their non-jetlagged peers. To understand why, the researchers delved deeper, examining the mice’s body clocks, which regulate daily biological rhythms. They measured clock gene activity in the liver and adrenal glands and tracked deep body temperature, a key indicator of circadian health. In female mice, chronic jet lag caused significant disruption to clock gene activity and weakened temperature rhythms. Male mice, however, displayed remarkably stable body clock function despite their metabolic changes.
This resilience in males piqued the team’s curiosity. In a follow-up experiment, they castrated male mice to remove testosterone and exposed them to the same jet lag conditions. The results mirrored those seen in females – perturbed body temperature, disrupted clock gene activity, and weight loss. When these castrated mice were given testosterone injections, their symptoms reversed, highlighting the hormone’s protective role. “Testosterone is therefore key to a resilient body clock in male mice,” Yasuo explained. “It also significantly impacts metabolism and how the body responds to glucose.”
The findings suggest that sex hormones like testosterone and, potentially, oestrogen play a critical role in how jet lag affects the body. For female mice, the weight loss raises intriguing questions. Yasuo speculated that it might stem from heightened sensitivity to stress or anxiety, though more research is needed to confirm this. The team also plans to investigate why jetlagged male mice gain weight despite minimal disruption to their body clocks, a puzzle that defies simple explanation.
For years, jet lag has been synonymous with fatigue, irritability, and metabolic woes, particularly for shift workers and frequent travellers. Professor Yasuo emphasised the real-world stakes. “Chronic jet lag, where a person’s body clock is consistently out of sync with natural day-night cycles, is a condition that affects many people, such as shift workers,” she said. “Chronic jet lag increases the risk of metabolic disorders, like obesity and diabetes, so understanding the biological effects of jet lag is very important.” Yet, human studies often struggle to isolate jet lag’s effects amid variables like diet, stress, and exercise. By using mice in controlled settings, the team sidestepped these complications.
Historically, animal research has skewed towards males, overlooking critical sex differences. “The biggest issue so far is that animal studies have typically focused only on males, yet over half of all shift workers, such as nurses, are women,” Yasuo noted. “So for me, it was important to look at female mice too.” This study marks a step towards addressing that gap, with implications that extend beyond the lab. As lifestyles grow increasingly irregular, tailoring health advice to account for sex could prove vital.
Looking ahead, the researchers aim to explore oestrogen’s influence on female body clocks and probe how jet lag alters appetite and food preferences. For now, their work serves as a reminder that biology is rarely one-size-fits-all. “Of course, human lifestyles are much more complicated,” Yasuo acknowledged. “Different people respond to stress in different ways, or have different dietary or exercise habits.” Even so, this research lights the way for more personalised approaches to managing jet lag’s toll.
