Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation

Stephanie J Mihalik, Sara F Michaliszyn, Javier de las Heras, Fida Bacha, SoJung Lee, Donald H Chace, Victor R DeJesus, Jerry Vockley, Silva A Arslanian, Stephanie J Mihalik, Sara F Michaliszyn, Javier de las Heras, Fida Bacha, SoJung Lee, Donald H Chace, Victor R DeJesus, Jerry Vockley, Silva A Arslanian

Abstract

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.

Figures

Figure 1
Figure 1
Plasma free carnitine and AcylCN concentrations in NW, OB, and type 2 diabetic (T2DM) subjects. P ANOVA among the three groups is shown above each species. Bonferroni post hoc analyses for significant (P < 0.05) differences between any two groups are indicated with the same letter.
Figure 2
Figure 2
Plasma amino acid concentrations in NW, OB, and type 2 diabetic (T2DM) subjects. P ANOVA among the three groups is shown above each species. Bonferroni post hoc analyses for significant (P < 0.05) differences between any two groups are indicated with the same letter.

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