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

IntroductionObestatin is a controversial gastrointestinal peptide purported to have metabolic actions.ObjectivesThis 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.MethodsUntargeted 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.ResultsIn 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 2α-(hydroxymethyl)-5α-androstane-3β,17β-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.ConclusionThis 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1063-0) contains supplementary material, which is available to authorized users.

Non-targeted LC-MS/MS metabolomic profiling of human plasma uncovers a novel Mediterranean diet biomarker panel

“…Peak picking thresholds were set between 0.5 and 20 min. A peak threshold lter of 2.5 AU was applied (15). Data was normalised to all compounds by correcting for multiple features to determine a global scaling factor.…”

“…Prior to sample analysis 10 pooled conditioning samples were injected. To determine chromatographic reproducibility of retention times and peak intensities, pooled samples were injected after every 10 sample injections throughout the experiment (14,15). Pooled samples were comprised of all plasma samples from the study and were subjected to the same extraction procedure applied to the individual plasma samples.…”

Non-targeted LC–MS/MS metabolomic profiling of human plasma uncovers a novel Mediterranean diet biomarker panel

“…Prior to sample analysis 10 pooled conditioning samples were injected. To determine chromatographic reproducibility of retention times and peak intensities, pooled samples were injected after every 10 sample injections throughout the experiment (Cowan et al, 2016 ; Graham et al, 2013 ). Pooled samples were comprised of all plasma samples from the study and were subjected to the same extraction procedure applied to the individual plasma samples.…”

Sensor of molecular imbalance in metabolic disorder: Determination of molecular behavior wired in disease utilizing metabolomics

“…Therefore, metabolomics is more advantageous than determining the pathologic structure of molecular behavior in ghrelin and leptin. Also, it can apply preventive benefi ts using microbiome behavioral interaction with adipose status, including an aspect of proliferation and differentiation by monitoring molecular-based cell imaging and by comparison detail between metabolites inside cells and outside cells using in adipose-derived stem cells or diet-induced obesity mice model with biomarker, a stable obestatin analog (PEG-OB(Cys10, Cys13)) [10,11].…”