• Suwen Li, Yan Wang, Zinan Li, Cong Long, Qian Zhou, and Qiu Chen.
• College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
• Medicine (Baltimore). 2022 Nov 25; 101 (47): e31261e31261.

Background And RationaleObesity is a metabolic condition brought on by the interplay of hereditary and environmental factors, making it one of the most common diseases in the world. Insulin resistance (IR) and obesity have a close connection and can both be advantageous. One of the main methods of epigenetic regulation is DNA methylation modification. Studies have demonstrated over the past few years that DNA methylation is crucial to the emergence of obesity and DNA methylation can lead to IR. Adipose tissue participates in the physiopathological processes of obesity and IR and functions as an endocrine organ controlling the body's balanced metabolism, thus, adipose tissue-associated gene DNA methylation affects the development of obesity and IR by influencing the function of adipose tissue. Hence, an explanation of current research on DNA methylation, IR, and obesity, following the most recent developments, exploring changes in DNA methylation in different types of adipose tissue in insulin-resistant patients and obese patients may enable the identification of novel targets in clinical obesity prevention and treatment.Method And AnalysisThe following electronic bibliographic databases will be searched from inception for peer-reviewed original research published: MEDLINE (through PubMed), Scopus, and EMBASE. Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception to December 31, 2021 will be conducted. Systematic reviews will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. The development of search strategies will make use of medical issue phrases and keywords associated with DNA methylation, Adipose tissue DNA methylation, obesity, and IR. Identified citations will be independently reviewed by two authors to determine eligibility at the title and abstract level, and then at the full text and data extraction phases. Disagreements and conflicts will be resolved through discussion with a third author. Two authors will extract the necessary data from the included studies independently, and The Cochrane Risk of Bias Assessment Tool will be used to assess the bias of randomized controlled studies, and the Newcastle-Ottawa scale for nonrandomized controlled studies. If the interventions and outcomes evaluated are sufficiently homogeneous, results from subgroups of studies will be pooled together in a meta-analysis.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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