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Acetylome Analyses Provide New Insights into the Effect of Chronic Intermittent Hypoxia on Hypothalamus-Dependent Endocrine Metabolism Impairment
by
,
Yaru Kong
1,2,3,†,
Jie Ji
4,†,
Xiaojun Zhan
3,†,
Weiheng Yan
1,2,3,
Fan Liu
1,2,5,
Pengfei Ye
3,
Shan Wang
5,* and
Jun Tai
1,3,* 1
Children’s Hospital Capital Institute of Paediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China
2
Graduate School of Peking Union Medical College, Beijing 100730, China
3
Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital Capital Institute of Paediatrics, Beijing 100020, China
4
Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
5
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Paediatrics, Beijing 100020, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biology 2024, 13(8), 559; https://doi.org/10.3390/biology13080559 (registering DOI)
Submission received: 11 June 2024
/
Revised: 17 July 2024
/
Accepted: 22 July 2024
/
Published: 24 July 2024
Simple Summary
Simple Summary: The incidence of obstructive sleep apnea in children is increasing year by year, and its occurrence and related metabolic and endocrine lesions may be related to hypothalamic dysfunction. Lysine acetylation is a common post-translational modification that is essential for metabolism. The aim of this study was to determine the effects of chronic intermittent hypoxia- induced lysine acetylation on hypothalamic function in an infant mice model, simulating pediatric obstructive sleep apnoea patients. Our study revealed the lysine acetylome and proteomic profile of the hypothalamus induced by chronic intermittent hypoxia in juvenile mice. Differentially acetylated proteins were involved in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Our findings suggest that chronic intermittent hypoxia may induce metabolic and endocrine dysregulation through modulation of hypothalamic lysine acetylation.
Abstract
Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 3 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Our analysis identified and quantified 2699 Kac sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant down-regulation of proteins that are known to be involved in endocrine hormone secretion. This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus as well as its potential role in endocrine impairment.
