Implanted Cells That Release Leptin Help Animals Recover From Jet Lag Faster, Study Finds

Researchers at Rice University, supported by the Rice Biotech Launch Pad, and Northwestern University have developed an implantable cell therapy that may help the body's internal clock adjust more quickly after jet lag or shift work. The study, published in Advanced Science, used encapsulated cells engineered to continuously release leptin, a metabolism-related hormone, and found the treatment shortened the time animals needed to adjust to simulated changes in the light-dark cycle.

The therapy uses human retinal pigment epithelial cells modified to produce leptin, enclosed inside microscopic alginate spheres that shield them from the immune system while letting the hormone reach the bloodstream. After a subcutaneous injection, the cells temporarily raise leptin levels before gradually losing viability. “Current approaches for adjusting circadian rhythms rely heavily on precisely timed behaviors such as light exposure, meal schedules or melatonin administration,” said Omid Veiseh, professor of bioengineering at Rice.

In mice, delaying their schedule by four hours, animals given the leptin-producing cells adapted 50% faster than untreated controls. In cynomolgus macaques, whose sleep-wake patterns resemble humans', the treatment was well tolerated and shortened adjustment after six-hour schedule changes by about one day versus controls, based on activity, heart rate and core body temperature. “The similar effects in rodents and primates suggest the underlying biology may be conserved across species,” said Fred Turek of Northwestern's Center for Sleep and Circadian Biology.

Blood testing found no significant toxicity in the macaques, including animals given multiple doses over one year. The treatment did not reduce total, REM or non-REM sleep, and after some schedule changes animals showed more slow-wave sleep, suggesting improved sleep quality. The cells worked for several days before naturally declining. “Our goal was not to permanently alter the circadian system,” said first author Samantha Fleury.

The researchers say the approach could eventually be studied for repeated disruptions such as shift work, military operations and international travel. “This work provides further evidence that metabolic pathways can be harnessed to influence circadian biology,” said Jonathan Rivnay of Northwestern, a senior author, adding that it shows how engineered cell therapies can deliver active molecules in ways hard to achieve through conventional dosing.