Research
Hormonal
Saturated fatty acids induce insulin resistance by activating TLR4, which drives the transcriptional upregulation of enzymes for de novo ceramide synthesis.
Saturated fats may trigger an inflammatory response (TLR4) that increases ceramide levels, blocking insulin. This suggests that the type of fat matters more than just the presence of fat, as unsaturated fats do not appear to trigger this specific pathway.
ModerateSupportsMEDIUM confidence
TLR4 was requisite for palmitate-induced insulin resistance and ceramide synthesis, while ceramide synthesis was requisite for TLR4-induced insulin resistance.
Why this rating
Based on rodent models and cell culture; human relevance is suggested but not definitively proven by interventional trials.
Source
Ceramides as modulators of cellular and whole-body metabolism
Benjamin T. Bikman et al. · Journal of Clinical Investigation · 2011
DOI 10.1172/jci57144
narrative_reviewCited 411×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Inhibition of de novo ceramide synthesis (via SPT inhibitors like myriocin or genetic knockdown) reverses insulin resistance and improves glucose tolerance in rodent models of obesity and high-fat feeding.Moderate
- Adiponectin improves metabolic health by activating ceramidase, which degrades ceramide and promotes the production of sphingosine-1-phosphate (S1P), thereby opposing ceramide's inhibitory effects on insulin signaling.Moderate
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