Hormonal
Rapid elevation of intramyocellular lipids (IMCL) via elevated circulating nonesterified fatty acids (NEFA) and hyperinsulinemia causes a significant decrease in skeletal muscle insulin sensitivity in healthy humans.
In healthy individuals, rapidly increasing the amount of fat circulating in your blood (via infusion or a very high-fat meal) while your insulin is high will quickly reduce your muscles' ability to use glucose. This happens because fat accumulates inside the muscle cells (IMCL). This suggests that chronic high-fat intake can impair insulin sensitivity through this mechanism.
In conclusion, this study showed that IMCL formation, induced rapidly through short-term elevation of circulating NEFA and hyperinsulinemia, leads to decreased insulin sensitivity.
Why this rating
Controlled clinical trial with rigorous measurement (glucose clamp and MRS) in healthy subjects, but limited generalizability to diabetic populations.
Source
Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans
Oliver Bachmann et al. · Diabetes · 2001
DOI 10.2337/diabetes.50.11.2579
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