Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men.
We hypothesized that an increased, incomplete fatty acid beta-oxidation in mitochondria could be part of the metabolic events leading to insulin resistance and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared with normal birth weight (NBW) individuals. Therefore, we measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5-day high-fat, high-calorie diet. We demonstrated that LBW men had higher C2 and C4-OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta-oxidation relative to the tricarboxylic acid cycle flux. Also, they had higher C6-DC, C10-OH/C8-DC, and total hydroxyl-/dicarboxyl-acylcarnitine levels, which may suggest an increased fatty acid omega-oxidation in the liver. Furthermore, LBW and NBW men decreased several acylcarnitine levels in response to overfeeding, which is likely a result of an upregulation of fatty acid oxidation due to the dietary challenge. Moreover, C10-OH/C8-DC and total hydroxyl-/dicarboxyl-acylcarnitine levels tended to be negatively associated with the serum insulin level, and the total hydroxyl-/dicarboxyl-acylcarnitine level additionally tended to be negatively associated with the hepatic insulin resistance index. This indicates that an increased fatty acid omega-oxidation could be a compensatory mechanism to prevent an accumulation of lipid species that impair insulin signaling.
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Amalie
A
Ribel-Madsen
Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Danish Diabetes Academy, Odense, Denmark.
Rasmus
R
Ribel-Madsen
Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Charlotte
C
Brøns
Sarah W. Stedman Nutrition and Metabolism, Center and Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Christopher B
CB
Newgard
Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Allan A
AA
Vaag
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark lih@bio.dtu.dk.
Lars I
LI
Hellgren
D000328:Adult; D001724:Birth Weight / Q000502:physiology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002952:Citric Acid Cycle / Q000502:physiology*; D018592:Cross-Over Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects* / Q000379:methods; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D002149:Energy Intake / Q000502:physiology; D005215:Fasting / Q000097:blood*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007230:Infant, Low Birth Weight / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D016032:Randomized Controlled Trials as Topic
D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; C116917:acylcarnitine; D002331:Carnitine
Acylcarnitines; high‐fat overfeeding; low birth weight; type 2 diabetes
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