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

Research output: Contribution to journalArticle

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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

Fingerprint

Carnitine
Blood Cells
Insulin Resistance
Palmitates
Hyperinsulinism
Type 2 Diabetes Mellitus
Adipose Tissue
Glucose Clamp Technique
Hyperlipidemias
Lipid Metabolism
Isotopes
Meals
Rodentia
Fatty Acids
Insulin

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

Palmitoyl-carnitine production by blood cells associates with the concentration of circulating acyl-carnitines in healthy overweight women. / Chondronikola, Maria; Asghar, Rabia; Zhang, Xiaojun; Dillon, Edgar; Durham, William J.; Wu, Zhanpin; Porter, Craig; Camacho-Hughes, Maria; Zhao, Yingxin; Brasier, Allan R.; Volpi, Elena; Sheffield-Moore, Melinda; Abate, Nicola; Sidossis, Labros; Tuvdendorj, Demidmaa.

In: Clinical Nutrition, 18.02.2016.

Research output: Contribution to journalArticle

Chondronikola, Maria ; Asghar, Rabia ; Zhang, Xiaojun ; Dillon, Edgar ; Durham, William J. ; Wu, Zhanpin ; Porter, Craig ; Camacho-Hughes, Maria ; Zhao, Yingxin ; Brasier, Allan R. ; Volpi, Elena ; Sheffield-Moore, Melinda ; Abate, Nicola ; Sidossis, Labros ; Tuvdendorj, Demidmaa. / Palmitoyl-carnitine production by blood cells associates with the concentration of circulating acyl-carnitines in healthy overweight women. In: Clinical Nutrition. 2016.
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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.",
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author = "Maria Chondronikola and Rabia Asghar and Xiaojun Zhang and Edgar Dillon and Durham, {William J.} and Zhanpin Wu and Craig Porter and Maria Camacho-Hughes and Yingxin Zhao and Brasier, {Allan R.} and Elena Volpi and Melinda Sheffield-Moore and Nicola Abate and Labros Sidossis and Demidmaa Tuvdendorj",
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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

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

PY - 2016/2/18

Y1 - 2016/2/18

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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