Intermittent fasting promotes type 3 innate lymphoid cells secreting IL-22 contributing to the beigeing of white adipose tissue
Hong Chen,
Lijun Sun,
Lu Feng,
Xue Han,
Yunhua Zhang,
Wenbo Zhai,
Zehe Zhang,
Michael Mulholland,
Weizhen Zhang,
Yue Yin
Affiliations
Hong Chen
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China; State Key Laboratory of Female Fertility Promote, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
Lijun Sun
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China
Lu Feng
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China
Xue Han
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China
Yunhua Zhang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China
Wenbo Zhai
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China
Zehe Zhang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China
Michael Mulholland
Department of Surgery, University of Michigan Medical Center, Ann Arbor, United States
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China; Department of Surgery, University of Michigan Medical Center, Ann Arbor, United States
Department of Pharmacology, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University, Beijing, China
Mechanism underlying the metabolic benefit of intermittent fasting remains largely unknown. Here, we reported that intermittent fasting promoted interleukin-22 (IL-22) production by type 3 innate lymphoid cells (ILC3s) and subsequent beigeing of subcutaneous white adipose tissue. Adoptive transfer of intestinal ILC3s increased beigeing of white adipose tissue in diet-induced-obese mice. Exogenous IL-22 significantly increased the beigeing of subcutaneous white adipose tissue. Deficiency of IL-22 receptor (IL-22R) attenuated the beigeing induced by intermittent fasting. Single-cell sequencing of sorted intestinal immune cells revealed that intermittent fasting increased aryl hydrocarbon receptor signaling in ILC3s. Analysis of cell-cell ligand receptor interactions indicated that intermittent fasting may stimulate the interaction of ILC3s with dendritic cells and macrophages. These results establish the role of intestinal ILC3s in beigeing of white adipose tissue, suggesting that ILC3/IL-22/IL-22R axis contributes to the metabolic benefit of intermittent fasting.
