ABSTRACT
The in situ metabolic profiling of the kidney is crucial to investigate the complex metabolic reprogramming underlying diabetic kidney disease (DKD) and to allow exploration of potential metabolic targets to improve kidney function. However, as the kidney is a highly heterogeneous organ, traditional metabolomic methods based on bulk analysis that produce an averaged measurement are inadequate. Herein, we employed an in situ metabolomics approach to discover alternations of DKD-associated metabolites and metabolic pathways. A series of histology-specific metabolic disturbances were discovered in situ using airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). In combination with integrated metabolomics analysis, five dysfunctional metabolic pathways were identified and located in the kidneys of type-2 DKD mice simultaneously for the first time, including taurine metabolism, arginine and proline metabolism, histidine metabolism, biosynthesis of unsaturated fatty acids, and fatty acid degradation pathways. As crucial nodes of metabolic pathways, five dysregulated rate-limiting enzymes related to altered metabolic pathways were further identified. These findings reveal alternations from metabolites to enzymes at the molecular level in the progression of DKD and provide insights into DKD-associated metabolic reprogramming.
ABSTRACT
Objective To detect the serum level of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF),a significant metabolite offish oil,in subjects with normal glucose tolerance (NGT) in local communities,and to investigate the association of CMPF with fatty acid metabolism.Methods A total of 272 NGT participants from screening for diabetes in Shanghai in 2013 were enrolled.Anthropometric measurements,biochemical evaluation,and questionnaire interview were performed for all the participants.The participants were divided into normal weight group [body mass index (BMI) ≤23.9 kg/m2,n =143] and overweight/obesity group (BMI ≥ 24 kg/m2,n =129).The serum CMPF concentrations were determined using an enzyme-linked immunosorbent assay.Results Serum CMPF level in overweight/obesity group was lower than that in normal weight group [96.50 (46.11,169.56) μmol/L vs 153.20 (83.16,282.97) μmol/L,P＜0.05].The serum CMPF level was negatively correlated with BMI (r =-0.256,P＜0.01),triglycerides (r =-0.175,P =0.004),and free fatty acid (r =-0.126,P =0.041) according to bivariate correlation analyses.A multivariate stepwise linear regression analysis showed that the serum CMPF level was independently associated with BMI,triglycerides,free fatty acid,and HbA1C.A logistic regression analysis showed that the CMPF was a protective factor against obesity (OR =0.324,95％ CI 0.158,0.664).Conclusion Serum CMPF level is reduced in overweight/obese subjects.CMPF is beneficial to lipid metabolism.
