TNF and Insulin resistance: Estrogen has also been heavily implicated in mediating the sexual dimorphism in metaflammation; OVX, ERα KO, and Aromatase KO mouse models have all shown that a reduction in circulating estrogen results in increased obesity-associated insulin resistance and metaflammation, with increases in pro-inflammatory ATMs and an upregulation of pro-inflammatory genes such as TNFα, IL-6, IL-1β, and MCP-1 [19,21,28,88,89,90,91].