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. 2013 Dec 6;12(12):5801-11.
doi: 10.1021/pr4008199. Epub 2013 Nov 18.

Very Low Carbohydrate Diet Significantly Alters the Serum Metabolic Profiles in Obese Subjects

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Free PMC article

Very Low Carbohydrate Diet Significantly Alters the Serum Metabolic Profiles in Obese Subjects

Yunjuan Gu et al. J Proteome Res. .
Free PMC article

Abstract

Emerging evidence has consistently shown that a very low carbohydrate diet (VLCD) can protect against the development of obesity, but the underlying mechanisms are not fully understood. Here we applied a comprehensive metabonomics approach using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to study the effects of an 8-week dietary intervention with VLCD on serum metabolic profiles in obese subjects. The VLCD intervention resulted in a weight loss and significantly decreased homeostasis model assessment-insulin resistance. The metabonomics analysis identified a number of differential serum metabolites (p < 0.05) primarily attributable to fatty acids, amino acids including branched chain amino acids, amines, lipids, carboxylic acids, and carbohydrates in obese subjects compared to healthy controls. The correlation analysis among time, VLCD intervention, and clinical parameters revealed that the changes of metabolites correlated with the changes of clinical parameters and showed differences in males and females. Fatty acids, amino acids, and carboxylic acids were increased in obese subjects compared with their normal healthy counterparts. Such increased levels of serum metabolites were attenuated after VLCD intake, suggesting that the health beneficial effects of VLCD are associated with attenuation of impaired fatty acid and amino acid metabolism. It also appears that VLCD induced significant metabolic alterations independent of the obesity-related metabolic changes. The altered metabolites in obese subjects post-VLCD intervention include arachidonate, cis-11,14-eicosadienoate, cis-11,14,17-eicosatrienoate, 2-aminobutyrate, acetyl-carnitine, and threonate, all of which are involved in inflammation and oxidation processes. The results revealed favorable shifts in fatty acids and amino acids after VLCD intake in obese subjects, which should be considered biomarkers for evaluating health beneficial effects of VLCD and similar dietary interventions.

Figures

Figure 1.
Figure 1.
(A) PCA and (B) OPLS-DA scores plot constructed with the 113 annotated metabolites.
Figure 2.
Figure 2.
OPLS-DA scores plot constructed with the 113 annotated metabolites.
Figure 3.
Figure 3.
(A) Heatmap shows changes in metabolites compared to healthy control at obesity subjects, obesity subjects after VLCD intervention at week four and eight. Shades of yellow and blue represent fold increase and fold decrease of a metabolite, respectively, in obesity subjects, obesity subjects after 4 weeks VLCD intervention or obesity subjects after 8 weeks VLCD intervention relative to healthy controls (see color scale); (B) metabolic pathways being affected by VLCD intervention; and (C) Venn diagramm exhibiting the commonly and specifically affected metabolites.
Figure 4.
Figure 4.
Heatmap shows interactions between time (metabolite change from baseline, 4 weeks, and then 8 weeks), VLCD intervention (4 weeks and 8 weeks) and clinical parameters. Shades of red and blue represent positive correlation and negative correlation, respectively (see color scale).
Figure 5.
Figure 5.
Heatmaps show the correlation of the change of metabolite with baseline (A) after 4 weeks VLCD intervention and (B) after 8 weeks VLCD intervention versus the changes in BMI, FPG, and FINS. Shades of red and blue represent positive correlation and negative correlation, respectively; in the change of metabolite in obesity subjects after 4 weeks VLCD intervention or obesity subjects after 8 weeks VLCD intervention relative to the changes of clinical parameters (see color scale).

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