Research
Hormonal
TNF and NF-κB signaling pathways directly inhibit insulin signaling by phosphorylating IRS-1, thereby causing insulin resistance; neutralizing TNF or inhibiting IKKβ improves glucose homeostasis.
Chronic inflammation in fat tissue directly blocks insulin's ability to work by interfering with key signaling proteins (IRS-1). Reducing this inflammation, whether through weight loss, exercise, or potentially anti-inflammatory strategies, can restore insulin sensitivity.
GoodSupportsHIGH confidence
TNF neutralisation improves glucose homeostasis and reduces diabetes risk in human patients... IKKβ directly phosphorylates and inhibits the insulin receptor substrate (IRS), an essential adaptor of the activated insulin receptor (IR)... resulting in a weak or null response to insulin.
Why this rating
Supported by multiple animal models and some human clinical trials (e.g., TNF neutralization).
Source
Cell death and inflammation during obesity: “Know my methods, WAT(son)”
Ximena Hildebrandt et al. · Cell Death and Differentiation · 2022
DOI 10.1038/s41418-022-01062-4
narrative_reviewCited 271×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Obesity induces low-grade chronic inflammation in white adipose tissue (WAT) via adipocyte death (apoptosis/necroptosis), which recruits pro-inflammatory macrophages (forming crown-like structures) and triggers systemic insulin resistance and metabolic syndrome.Good
- Different forms of cell death (apoptosis, necroptosis, pyroptosis) in adipose tissue have distinct inflammatory consequences; necroptosis is highly inflammatory and linked to metabolic dysfunction, while apoptosis may trigger anti-inflammatory macrophage responses.Moderate
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