Encapsulated Leptin‐Producing Cells Facilitate Entrainment of Circadian Rhythms in Rodents and Nonhuman Primates
7 affiliations
- 1Department of Bioengineering Rice University Houston Texas USA
- 2Center for Sleep and Circadian Biology Northwestern University Evanston Illinois USA
- 3Department of Neurobiology Weinberg College of Arts and Sciences Northwestern University Evanston Illinois USA
- 4CellTrans Inc. Chicago Illinois USA
- 5Department of Visceral and Transplant Surgery University of Zurich Zürich Switzerland
- 6Department of Biomedical Engineering McCormick School of Engineering Northwestern University Evanston Illinois USA
- 7Department of Materials Science and Engineering McCormick School of Engineering Northwestern University Evanston Illinois USA
Abstract
Both the timing and composition of food intake have gained recognition for their effects on circadian (daily) rhythms in mammals, however the mechanisms by which these effects are exerted are incompletely understood. The present studies focus on synchronization of circadian rhythms to the environmental light‐dark cycle, particularly re‐entrainment following a phase shift such as occurs with travel across time zones or shift work. To examine the role and therapeutic potential of the peptide hormone leptin in these effects, we create and characterize injectable leptin factories consisting of encapsulated human retinal pigment epithelium (RPE) cells engineered to constitutively produce leptin. Subcutaneous injections of these leptin factories result in sustained elevation of blood leptin over more than a day, and accelerate entrainment to both phase delays and phase advances. Leptin factory administration to diurnal cynomolgus macaques is safe and effectively reduced entrainment rate by approximately 1 day. In addition, capsule administration in cynomolgus macaques has no demonstrable adverse effects on sleep, increasing Non‐Rapid Eye Movement sleep (NREM sleep) slow‐wave energy. Taken together, these results implicate metabolic regulation as a novel approach to accelerating adaptation to changing schedules and suggest that leptin can be used to therapeutically decrease entrainment time.
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BibTeX
@article{fleury2026encapsulated,
title = {{Encapsulated Leptin‐Producing Cells Facilitate Entrainment of Circadian Rhythms in Rodents and Nonhuman Primates}},
author = {Samantha T. Fleury and Xuanyi Lin and Peter D. Rios and Christopher Olker and Eun Joo Song and Alejandra Cobos Perez and Cody Fell and Daisy Lopez and Ira Joshi and Hafsa Nasir and Cecelia Curtis and Danna Muringi and Kaiyuan Wang and José Oberholzer and Fred W. Turek and Isaac B. Hilton and Jonathan Rivnay and Martha Hotz Vitaterna and Omid Veiseh},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.77191},
url = {https://doi.org/10.1002/advs.77191},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Encapsulated Leptin‐Producing Cells Facilitate Entrainment of Circadian Rhythms in Rodents and Nonhuman Primates
AU - Samantha T. Fleury
AU - Xuanyi Lin
AU - Peter D. Rios
AU - Christopher Olker
AU - Eun Joo Song
AU - Alejandra Cobos Perez
AU - Cody Fell
AU - Daisy Lopez
AU - Ira Joshi
AU - Hafsa Nasir
AU - Cecelia Curtis
AU - Danna Muringi
AU - Kaiyuan Wang
AU - José Oberholzer
AU - Fred W. Turek
AU - Isaac B. Hilton
AU - Jonathan Rivnay
AU - Martha Hotz Vitaterna
AU - Omid Veiseh
PY - 2026
DA - 2026/08/13
JO - Advanced Science
DO - 10.1002/advs.77191
UR - https://doi.org/10.1002/advs.77191
AB - Both the timing and composition of food intake have gained recognition for their effects on circadian (daily) rhythms in mammals, however the mechanisms by which these effects are exerted are incompletely understood. The present studies focus on synchronization of circadian rhythms to the environmental light‐dark cycle, particularly re‐entrainment following a phase shift such as occurs with travel across time zones or shift work. To examine the role and therapeutic potential of the peptide hormone leptin in these effects, we create and characterize injectable leptin factories consisting of encapsulated human retinal pigment epithelium (RPE) cells engineered to constitutively produce leptin. Subcutaneous injections of these leptin factories result in sustained elevation of blood leptin over more than a day, and accelerate entrainment to both phase delays and phase advances. Leptin factory administration to diurnal cynomolgus macaques is safe and effectively reduced entrainment rate by approximately 1 day. In addition, capsule administration in cynomolgus macaques has no demonstrable adverse effects on sleep, increasing Non‐Rapid Eye Movement sleep (NREM sleep) slow‐wave energy. Taken together, these results implicate metabolic regulation as a novel approach to accelerating adaptation to changing schedules and suggest that leptin can be used to therapeutically decrease entrainment time.
SN - 2198-3844
ER -