(OR17-03-26) Lean Mass as a Predictor of Dietary Fatty Acid Trafficking in Humans

Objectives: After meals, chylomicron-triacylglycerols (TG) interact with endothelial-bound lipoprotein lipase to deliver dietary fatty acids to the body. A process called ‘spillover’ occurs when intravascular lipolysis exceeds the rate of tissue uptake. Elevated FFA from spillover contribute to the development of ectopic lipid deposition. Here, data were analyzed from five human studies to investigate the impact of lean mass on spillover in subjects who were healthy or had metabolic diseases. Plasma acylcarnitines (AC), also measured, provide evidence of fatty acid entry into and out of tissues and their mitochondria. We tested whether AC, an indicator of tissue fatty acid flux, would be inversely related to spillover.

Methods: Subjects (40M/41F) were characterized as healthy (n=15, BMI: 24.3±2.5 kg/m², fasting insulin: 5.0±3.0 µU/mL), insulin resistant (n=33, 34.8±6.5 kg/m², 9.1±4.2 µU/mL), or having obesity associated diseases (n=33, 38.1±7.1 kg/m², 17.8±9.7 µU/mL). Stable isotope-labeled, high-fat meals allowed for the quantification of nocturnal and postprandial dietary fatty acid kinetics.

Results: After consuming two meals, subjects were ranked after each meal based on the magnitude of postprandial spillover. High or low levels of spillover were consistently found in the same individuals (r=0.575, P=0.003). Spillover and AC were inversely related (r=-0.812, P=0.001) and the two demonstrated opposite relationships with lean mass (r=-0.392, P < 0.001 and r=0.684, P=0.004, respectively). The latter finding supports the measurement of both spillover and AC to predict muscle fatty acid flux. We also demonstrated for the first time.

Conclusions: Spillover is an inherent characteristic of an individual, and concentrations represent lipolyzed dietary-TG not immediately taken up by tissues. By contrast, plasma AC represent evidence of tissue fatty acid uptake (e.g., muscle), mitochondrial entry, and release back into plasma. This is the first integration of these two measurements which demonstrates that their combined use provides a non-invasive, yet comprehensive assessment of dietary fatty acid trafficking in humans.

Funding Sources: NIH-NIDDK, American Diabetes Association, International Life Sciences Institute, The Allen Foundation