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



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).



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.
Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; Metabolism Unit, Shriners Hospitals for Children, Galveston, TX 77555, USA.
Maria
M
Chondronikola
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Rabia
R
Asghar
Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
Xiaojun
X
Zhang
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Edgar L
EL
Dillon
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
William J
WJ
Durham
Zoex Corporation, Houston, TX 77034, USA.
Zhanpin
Z
Wu
Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; Metabolism Unit, Shriners Hospitals for Children, Galveston, TX 77555, USA.
Craig
C
Porter
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Maria
M
Camacho-Hughes
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Yingxin
Y
Zhao
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Allan R
AR
Brasier
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Elena
E
Volpi
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Melinda
M
Sheffield-Moore
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Nicola
N
Abate
Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; Metabolism Unit, Shriners Hospitals for Children, Galveston, TX 77555, USA.
Labros
L
Sidossis
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: detuvden@utmb.edu.
Demidmaa
D
Tuvdendorj
D000328:Adult; D000368:Aged; D001773:Blood Cells / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008875:Middle Aged; D050177:Overweight / Q000097:blood*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000097:blood; D010172:Palmitoylcarnitine / Q000096:biosynthesis* / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D010168:Palmitates; C116917:acylcarnitine; D010172:Palmitoylcarnitine; D002331:Carnitine
Acyl-carnitines; Blood cells; Insulin resistance; Plasma palmitate oxidation; Stable isotope tracer