Palmitoyl-carnitine production by blood cells associates with the concentration of circulating acyl-carnitines in healthy overweight women

Maria Chondronikola, Rabia Asghar, Xiaojun Zhang, Edgar Dillon, William J. Durham, Zhanpin Wu, Craig Porter, Maria Camacho-Hughes, Yingxin Zhao, Allan R. Brasier, Elena Volpi, Melinda Sheffield-Moore, Nicola Abate, Labros Sidossis, Demidmaa Tuvdendorj

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2 Scopus citations

Abstract

Background: Circulating acyl-carnitines (acyl-CNTs) are associated with insulin resistance (IR) and type 2 diabetes (T2D) in both rodents and humans. However, the mechanisms whereby circulating acyl-CNTs are increased in these conditions and their role in whole-body metabolism remains unknown. The purpose of this study was to determine if, in humans, blood cells contribute in production of circulating acyl-CNTs and associate with whole-body fat metabolism. Methods and results: Eight non-diabetic healthy women (age: 47 ± 19 y; BMI: 26 ± 1 kg·m-2) underwent stable isotope tracer infusion and hyperinsulinemic-euglycemic clamp study to determine in vivo whole-body fatty acid flux and insulin sensitivity. Blood samples collected at baseline (0 min) and after 3 h of clamp were used to determine the synthesis rate of palmitoyl-carnitine (palmitoyl-CNT) in vitro. The fractional synthesis rate of palmitoyl-CNT was significantly higher during hyperinsulinemia (0.788 ± 0.084 vs. 0.318 ± 0.012%·hr-1, p = 0.001); however, the absolute synthesis rate (ASR) did not differ between the periods (p = 0.809) due to ∼30% decrease in blood palmitoyl-CNT concentration (p = 0.189) during hyperinsulinemia. The ASR of palmitoyl-CNT significantly correlated with the concentration of acyl-CNTs in basal (r = 0.992, p < 0.001) and insulin (r = 0.919, p = 0.001) periods; and the basal ASR significantly correlated with plasma palmitate oxidation (r = 0.764, p = 0.027). Conclusion: In women, blood cells contribute to plasma acyl-CNT levels and the acyl-CNT production is linked to plasma palmitate oxidation, a marker of whole-body fat metabolism. Future studies are needed to confirm the role of blood cells in acyl-CNT and lipid metabolism under different physiological (i.e., in response to meal) and pathological (i.e., hyperlipidemia, IR and T2D) conditions.

Original languageEnglish (US)
JournalClinical Nutrition
DOIs
StateAccepted/In press - Feb 18 2016

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Keywords

  • Acyl-carnitines
  • Blood cells
  • Insulin resistance
  • Plasma palmitate oxidation
  • Stable isotope tracer

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Critical Care and Intensive Care Medicine

Cite this

Chondronikola, M., Asghar, R., Zhang, X., Dillon, E., Durham, W. J., Wu, Z., Porter, C., Camacho-Hughes, M., Zhao, Y., Brasier, A. R., Volpi, E., Sheffield-Moore, M., Abate, N., Sidossis, L., & Tuvdendorj, D. (Accepted/In press). Palmitoyl-carnitine production by blood cells associates with the concentration of circulating acyl-carnitines in healthy overweight women. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2016.08.019