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Metabolomic Profiling of Fatty Acid and Amino Acid Metabolism in Youth With Obesity and Type 2 Diabetes: Evidence for enhanced mitochondrial oxidation

OBJECTIVE: We compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents. RESEARCH DESIGN AND METHODS: Fasting plasma was analyzed by tandem mass spe...

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Detalles Bibliográficos
Autores principales: Mihalik, Stephanie J., Michaliszyn, Sara F., de las Heras, Javier, Bacha, Fida, Lee, SoJung, Chace, Donald H., DeJesus, Victor R., Vockley, Jerry, Arslanian, Silva A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322714/
https://www.ncbi.nlm.nih.gov/pubmed/22266733
http://dx.doi.org/10.2337/DC11-1577
Descripción
Sumario:OBJECTIVE: We compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents. RESEARCH DESIGN AND METHODS: Fasting plasma was analyzed by tandem mass spectrometry, body composition by dual energy X-ray absorptiometry and computed tomography, and total-body lipolysis and substrate oxidation by [(2)H(5)]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp. RESULTS: Long-chain AcylCNs (C18:2-CN to C14:0-CN) were similar among the three groups. Medium- to short-chain AcylCNs (except C8 and C10) were significantly lower in type 2 diabetes compared with NW, and when compared with OB, C2-, C6-, and C10-CN were lower. Amino acid concentrations were lower in type 2 diabetes compared with NW. Fasting lipolysis and FOX were higher in OB and type 2 diabetes compared with NW, and the negative association of FOX to C10:1 disappeared after controlling for adiposity, Tanner stage, and sex. IS was lower in OB and type 2 diabetes with positive associations between IS and arginine, histidine, and serine after adjusting for adiposity, Tanner stage, and sex. CONCLUSIONS: These metabolomics results, together with the increased rates of in vivo FOX, are not supportive of defective fatty acid or amino acid metabolism in obesity and type 2 diabetes in youth. Such observations are consistent with early adaptive metabolic plasticity in youth, which over time—with continued obesity and aging—may become dysfunctional, as observed in adults.