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the enhanced polarization of M1 macrophages and suppression of FOXP3+ regulatory T cells enhance inflammatory response in individuals with obesity and cause immune tolerance defect ( 5.2.2 Sexual hormone level disruption Under normal conditions, estrogen(E 2 ) undergoes two successive phases of metabolism: cytochrome P450 enzymes (such as CYP1A1) first metabolize E 2 into reactive metabolites (2-hydroxyestrogens and 4-hydroxyestrogens), which are then conjugated by sulfotransferase (SULT1E1) and UDP-glucuronosyltransferase (UGT2B7) to add a sulfonate (SO 3 - ) group and a glucuronide group, respectively (58)

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