1. Impaired IL-27 signaling aggravates macrophage senescence and sensitizes premature ovarian insufficiency induction by high-fat diet.
- Author
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Zhang XY, Wang CJ, Shen HH, Jiang F, Shi JL, Wang WJ, and Li MQ
- Subjects
- Adult, Animals, Female, Humans, Mice, Cellular Senescence, Interleukins metabolism, Mice, Inbred C57BL, Mice, Knockout, Ovary metabolism, Ovary pathology, Diet, High-Fat adverse effects, Macrophages metabolism, Macrophages immunology, Primary Ovarian Insufficiency pathology, Primary Ovarian Insufficiency metabolism, Primary Ovarian Insufficiency immunology, Receptors, Interleukin metabolism, Receptors, Interleukin genetics, Signal Transduction
- Abstract
Premature ovarian insufficiency (POI) critically affects female reproductive health, with obesity being a significant and recognized risk factor. Interleukin-27 (IL-27), known for its role in immune modulation and inflammation, has garnered attention in metabolic syndrome research. Nonetheless, the role of these immunometabolic factors on the initiation of POI remains to be unraveled. Our investigation delves into the influence of impaired IL-27 signaling on POI induction, particularly under the challenge of a high-fat diet (HFD). We analyzed patients' serum profiles and established a correlation of increased serum triglycerides with decreased IL-27 levels in POI cases. Experiments on C57BL/6 mice lacking the IL-27 receptor alpha (Il27ra
-/- ) revealed that when subjected to HFD, these mice developed hallmark POI symptoms. This includes escalated lipid deposition in both liver and ovarian tissues, increased ovarian macrophages cellular aging, and diminished follicle count, all pointing to compromised ovarian function. These findings unveil a novel pathway wherein impaired IL-27 signaling potentiates the onset of POI in the presence of HFD. Understanding the intricate interplay between IL-27, metabolic alterations, and immune dysregulation sheds light on potential therapeutic avenues for managing POI, offering hope for improved reproductive health outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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