Research
Hormonal
TNF-α and IL-6 are pro-inflammatory adipokines that contribute to insulin resistance by interfering with insulin signaling pathways, such as through JNK1-mediated serine phosphorylation of IRS-1.
Chronic low-grade inflammation from fat tissue releases TNF-α and IL-6, which can interfere with how insulin signals cells. While this is a key mechanism in animals, simply blocking these markers in humans has not consistently worked, suggesting a more complex interplay.
ModerateSupportsMEDIUM confidence
TNF-α and IL-6 modulate insulin resistance through several distinct mechanisms, including c-Jun N-terminal kinase 1 (JNK1)-mediated serine phosphorylation of IRS-1, IκB kinase (IKK)-mediated nuclear factor-κB (NF-κB) activation, and induction of SOCS-3 (164).
Why this rating
Strong mechanistic data in rodents, but human interventional trials (neutralizing antibodies) have failed to consistently improve insulin sensitivity.
Source
Adipokines and Insulin Resistance
Katja Rabe et al. · Molecular Medicine · 2008
DOI 10.2119/2008-00058.rabe
narrative_reviewCited 805×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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