Research
Hormonal
Ectopic lipid accumulation in non-adipose tissues (liver, muscle) causes insulin resistance primarily through diacylglycerol and ceramide signaling, not triglyceride storage itself.
Insulin resistance in obesity is driven by specific fat molecules (DAG and ceramide) that interfere with insulin signaling, not just the total amount of fat stored in organs.
StrongSupportsVERY_HIGH confidence
Current evidence argues against triglyceride itself being the culprit in these fatty-acid-mediated actions. Rather, strong evidence supports a role for diacylglycerol in the blunting of insulin signaling... ceramide... activate protein phosphatase 2A, which dephosphorylates and thus inactivates Akt/PKB.
Why this rating
Strong evidence cited from multiple studies showing causal links between DAG/ceramide and insulin resistance.
Source
Adipocyte metabolism and obesity
Alan Attie et al. · Journal of Lipid Research · 2008
DOI 10.1194/jlr.r800057-jlr200
narrative_reviewCited 219×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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