Fat-overload cell damage
Lipotoxic cell death↓
Also searched as Lipotoxic cell death.
This is the end of the chain, not a lever. Every driver placed here works by preventing the upstream damage rather than blocking the death step itself.
In depth
Fat-overload cell damage — the point at which fat overload stops being a metabolic problem and starts harming the cell itself.
What drives it
Ceramide load increases it.
PMC19389 — Ceramide is the messenger that carries the instruction to die when a cell is overloaded with saturated fat. Verbatim from the adiponectin-receptor work: 'Ceramidase activity is impaired in cells lacking both adiponectin receptor isoforms, leading to elevated ceramide levels and enhanced susceptibility to palmitate-induced cell death.' The reverse holds too - sulforaphane 'alleviated PA-mediated apoptosis, downregulated the expressions of cleaved caspase 3, as well as reduced ceramide contents' in the same experiment, and Ganoderma lucidum extract improved viability and decreased tunel staining in palmitate-stressed primary hepatocytes. Scope, stated: this is cell and rodent work. And the naming is deliberate - this pathway is fat-driven cell death specifically, not apoptosis in general, which the acb blend drives up as an anti-cancer aim. The two must never be conflated.
Eases ER stress increases it.
10.1371/journal.pone.0097868 — The unfolded protein response is the route by which lipid overload becomes cell death. Verbatim: alpha-linolenic acid 'prevents endoplasmic reticulum stress-mediated apoptosis of stearic acid lipotoxicity on primary rat hepatocytes' - it 'distinctly reduced cell death and levels of all three indicators of ER stress'. The pro-apoptotic arm is named in the same literature: palmitate drives 'nuclear translocation of pro-apoptotic C/EBP-homologous-protein-10 (CHOP)'. primary hepatocytes and hepatoma cells. Note this edge is a sequence, not a synonym - relieving ER strain is upstream of preventing the death, and a driver graded on one is not automatically graded on the other. doi 10.1371/journal.pone.0097868
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.