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Treatment of lean and diet-induced obesity (DIO) mice with a novel stable obestatin analogue alters plasma metabolite levels as detected by untargeted LC-MS metabolomics

ABSTRACT: Introduction: Obestatin is a controversial gastrointestinal peptide purported to have metabolic actions. Objectives: This study investigated whether treatment with a stable obestatin analogue (PEG-OB(Cys10, Cys13) changed plasma metabolite levels firstly in lean and subsequently in diet-induced obesity (DIO) C57BL6/J mice. Method: Untargeted LC-HRMS metabolomics experiments were carried out in ESI+ mode with plasma extracts from both groups of animals. Data were normalised, multivariate and univariate statistical analysis performed and metabolites of interest putatively identified. Result: In lean mice, 39 metabolites were significantly changed by obestatin treatment and the majority of these were increased, including various C16 and C18 moieties of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and monoacylglycerol, along with vitamin A, vitamin D3, tyrosine, acetylcarnitine and 2alpha-(hydroxymethyl)-5alpha-androstane-3beta,17beta-diol. Decreased concentrations of glycolithocholic acid, 3-dehydroteasterone and various phospholipids were observed. In DIO mice, 25 metabolites were significantly affected and strikingly, the magnitudes of changes here were generally much greater in DIO mice than in lean mice, and in contrast, the majority of metabolite changes were decreases. Four metabolites affected in both groups included glycolithocholic acid, and three different long-chain (C18) phospholipid molecules (phosphatidylethanolamine, platelet activating factor (PAF), and monoacylglycerol). Metabolites exclusively affected in DIO mice included various phosphatidylcholines, lysophosphatidylcholines and fatty acyls, as well as creatine and oxidised glutathione. Conclusion: This investigation demonstrates that obestatin treatment affects phospholipid turnover and influences lipid homeostasis, whilst providing convincing evidence that obestatin may be acting to ameliorate diet-induced impairments in lipid metabolism, and it may influence steroid, bile acid, PAF and glutathione metabolism.

INSTRUMENT(S): Orbitrap Elite (Thermo Scientific)

SUBMITTER: Elaine Cowan

PROVIDER: MTBLS334 | MetaboLights | 2017-07-25

REPOSITORIES: MetaboLights

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Treatment of lean and diet-induced obesity (DIO) mice with a novel stable obestatin analogue alters plasma metabolite levels as detected by untargeted LC-MS metabolomics.

Cowan Elaine E Kumar Praveen P Burch Kerry J KJ Grieve David J DJ Green Brian D BD Graham Stewart F SF

Metabolomics : Official journal of the Metabolomic Society 20160705

<h4>Introduction</h4>Obestatin is a controversial gastrointestinal peptide purported to have metabolic actions.<h4>Objectives</h4>This study investigated whether treatment with a stable obestatin analogue (PEG-OB(Cys<sup>10</sup>, Cys<sup>13</sup>)) changed plasma metabolite levels firstly in lean and subsequently in diet-induced obesity (DIO) C57BL6/J mice.<h4>Methods</h4>Untargeted LC-HRMS metabolomics experiments were carried out in ESI + mode with plasma extracts from both groups of animals. ...[more]

PMID: 27471436

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			Action	DRS
	MTBLS334	Other
	FILES	Other
	a_MTBLS334_lean_peg-ob_cys10_cys13.txt	Txt
	a_MTBLS334_obese_peg-ob_cys10_cys13.txt	Txt
	i_Investigation.txt	Txt