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Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

Wopereis S, Rubingh CM, van Erk MJ, Verheij ER, van Vliet T, Cnubben NH, Smilde AK, van der Greef J, van Ommen B, Hendriks HF - PLoS ONE (2009)

Bottom Line: Novel tools to understand these processes are needed.Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test.

View Article: PubMed Central - PubMed

Affiliation: Department Quality of Life, TNO, Zeist, the Netherlands. suzan.wopereis@tno.nl

ABSTRACT

Background: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.

Methodology: To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation.

Conclusions: Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.

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OGTT time course mean metabolite response with standard error on day 9 corrected for concentrations on day 0 for subjects on placebo and diclofenac treatment.A) for the metabolite isoleucine that contributes to treatment differences over the whole time course and B) for the metabolite glycine that contributes to treatment differences only in the second part of the time course. Legend to Figure 2: Dashed line: Diclofenac treated subjects; Solid line: Placebo treated subjects.
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pone-0004525-g002: OGTT time course mean metabolite response with standard error on day 9 corrected for concentrations on day 0 for subjects on placebo and diclofenac treatment.A) for the metabolite isoleucine that contributes to treatment differences over the whole time course and B) for the metabolite glycine that contributes to treatment differences only in the second part of the time course. Legend to Figure 2: Dashed line: Diclofenac treated subjects; Solid line: Placebo treated subjects.

Mentions: Only identified metabolites are shown in Table 4. The column ‘response type’ refers to Figure 2; metabolites with response type A showed a treatment difference over the whole time course and metabolites with response type B showed a treatment difference only in the second part of the time course (a response of the metabolite in the placebo group, whereas no change in the diclofenac treated group). For metabolites with response type B the mean is calculated over the time points with a treatment difference.


Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

Wopereis S, Rubingh CM, van Erk MJ, Verheij ER, van Vliet T, Cnubben NH, Smilde AK, van der Greef J, van Ommen B, Hendriks HF - PLoS ONE (2009)

OGTT time course mean metabolite response with standard error on day 9 corrected for concentrations on day 0 for subjects on placebo and diclofenac treatment.A) for the metabolite isoleucine that contributes to treatment differences over the whole time course and B) for the metabolite glycine that contributes to treatment differences only in the second part of the time course. Legend to Figure 2: Dashed line: Diclofenac treated subjects; Solid line: Placebo treated subjects.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2643463&req=5

pone-0004525-g002: OGTT time course mean metabolite response with standard error on day 9 corrected for concentrations on day 0 for subjects on placebo and diclofenac treatment.A) for the metabolite isoleucine that contributes to treatment differences over the whole time course and B) for the metabolite glycine that contributes to treatment differences only in the second part of the time course. Legend to Figure 2: Dashed line: Diclofenac treated subjects; Solid line: Placebo treated subjects.
Mentions: Only identified metabolites are shown in Table 4. The column ‘response type’ refers to Figure 2; metabolites with response type A showed a treatment difference over the whole time course and metabolites with response type B showed a treatment difference only in the second part of the time course (a response of the metabolite in the placebo group, whereas no change in the diclofenac treated group). For metabolites with response type B the mean is calculated over the time points with a treatment difference.

Bottom Line: Novel tools to understand these processes are needed.Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test.

View Article: PubMed Central - PubMed

Affiliation: Department Quality of Life, TNO, Zeist, the Netherlands. suzan.wopereis@tno.nl

ABSTRACT

Background: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.

Methodology: To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation.

Conclusions: Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.

Show MeSH
Related in: MedlinePlus