Hormonal
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.
This research suggests that high levels of ceramides, often resulting from saturated fat intake and obesity, actively block insulin signaling. While this study used drug inhibitors in mice, it implies that reducing saturated fat intake or managing lipid metabolism might be crucial for improving insulin sensitivity in humans, beyond just calorie counting.
pharmacological or genetic inhibition of enzymes required for de novo ceramide synthesis (i.e., SPT, CerS, and Des1) exerts a potent effect on cellular energetics and metabolism... these manipulations improve postprandial glucose tolerance and reverse insulin resistance caused by glucocorticoids, saturated fatty acids, inflammation, high-fat feeding, and leptin deficiency.
Why this rating
Evidence is derived from rodent models (ZDF rats, DIO mice) and cell cultures; human data is described as correlational.
Source
Ceramides as modulators of cellular and whole-body metabolism
Benjamin T. Bikman et al. · Journal of Clinical Investigation · 2011
DOI 10.1172/jci57144
More from this paper
- Saturated fatty acids induce insulin resistance by activating TLR4, which drives the transcriptional upregulation of enzymes for de novo ceramide synthesis.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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