Metabolomics

Dataset Information

6

Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes (Mouse data)


ABSTRACT: Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols (TAGs) with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined, offer unique opportunities to address this challenge. Therefore, we compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR) mutations with healthy controls. The absence of significant differences in TAG species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of TAGs with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of TAG species is indicative of increased de novo lipogenesis (DNL). To test this we investigated the distribution of these TAGs in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these TAGs with VLDL particles, and hence release of TAGs into the blood from the liver. To test further the hepatic origin of these TAGs we induced DNL in the mouse, comparing ob/ob and wild type mice on a chow or high fat diet, confirming that DNL induced an increase in relatively shorter, more saturated fatty acids. Overall, these studies highlight DNL in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue.

The protocols and data for mice samples are reported in current study MTBLS327.
The protocols and data for human samples are reported in study MTBLS162.

INSTRUMENT(S): Exactive (Thermo Scientific)

SUBMITTER: Jules Griffin  

PROVIDER: MTBLS327 | MetaboLights | 2017-03-02

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS327 Other
13073_2015_179_MOESM1_ESM.docx Other
20121128a__001__06__XW.raw Raw
20121128a__001__07__XW.raw Raw
20121128a__001__08__XW.raw Raw
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<h4>Background</h4>Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge.<h4>Methods</h4>We compared metabolite prof  ...[more]

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