TY - JOUR
T1 - Palmitoyl-carnitine production by blood cells associates with the concentration of circulating acyl-carnitines in healthy overweight women
AU - Chondronikola, Maria
AU - Asghar, Rabia
AU - Zhang, Xiaojun
AU - Dillon, Edgar L.
AU - Durham, William J.
AU - Wu, Zhanpin
AU - Porter, Craig
AU - Camacho-Hughes, Maria
AU - Zhao, Yingxin
AU - Brasier, Allan R.
AU - Volpi, Elena
AU - Sheffield-Moore, Melinda
AU - Abate, Nicola
AU - Sidossis, Labros
AU - Tuvdendorj, Demidmaa
N1 - Publisher Copyright:
© 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Acyl-carnitines
KW - Blood cells
KW - Insulin resistance
KW - Plasma palmitate oxidation
KW - Stable isotope tracer
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U2 - 10.1016/j.clnu.2016.08.019
DO - 10.1016/j.clnu.2016.08.019
M3 - Article
C2 - 27624997
AN - SCOPUS:84995484478
SN - 0261-5614
VL - 36
SP - 1310
EP - 1319
JO - Clinical Nutrition
JF - Clinical Nutrition
IS - 5
ER -