GPR120, an ω-3 fatty acid receptor, is seen as a potential target in diabetes and obesity research enabling indirect control of glucagon-like-peptide-1 (GLP-1) and thus affecting insulin secretion. Previous studies have shown GPR120 mediates insulin sensitization and possesses anti-diabetic properties due to its repression of macrophage-mediated inflammation, a key mechanism for insulin resistance. The study also showed a minor impairment of glucose tolerance and a significant increase in insulin secretion in knock-out (KO) animals (Oh DY et al., 2010). It has also been reported that GPR120 is crucial in energy balance control in rodents and humans and its expression is increased in adipose tissue of obese individuals (Ichimura A et al., 2012). A metabonomic approach was employed to determine metabolite changes between male, GPR120 wild-type (WT) and KO mice. GPR120 was knocked-out on a C57Bl/6 genetic background (AstraZeneca, Mölndal). This study aimed to determine whether the metabolic pathways affected by GPR120 KO could be identified. Mice were maintained on regular chow diet for 16 weeks before urine samples were collected from metabolically unchallenged animals. The samples were analysed using an integrated liquid chromatography-mass spectrometry (LC-MS) system (Waters, micro Q-TOF) in both positive and negative ionisation mode and the results processed through multivariate statistical analysis and principal components analysis (PCA) (MarkerLynx and Extended Statistics). Both unsupervised and supervised model plots from PCA showed discrete separation between the WT and KO groups of mice in urine samples. The perturbed metabolites were then statistically validated in accordance with FDA biomarker discovery regulations. From positive ionisation mode, three significantly perturbed ions were identified as causing the metabolite profile differences (ions = 204.1269 m/z, 298.0911 m/z and 339.0597 m/z). In negative ionisation mode, three different ions were identified as causing the main separation of metabolite profiles (ions = 519.9712 m/z, 203.9919 m/z and 269.0130 m/z). Ongoing analysis is being carried out to ascertain the identities of these ions.