Lipidomic Profiling on Oxidized Phospholipids in Type 2 Diabetes Mellitus Model Zebrafish

Abstract

Type 2 diabetes mellitus is a serious metabolic disorder in the world. Oxidative stress, as a key role on the pathogenesis of diabetes, also results in the oxidation of phospholipids. However, studies on phospholipid oxidation in diabetes, especially directly focusing on oxidized and degraded phospholipid species, are quite limited. In this study, phospholipid profiles of diabetic zebrafish plasma were characterized by LC-HRMS and MS/MS, and the total amounts of each lipid class were compared. Furthermore, the key molecular species as biomarkers in distinguishing control and diabetic samples were investigated by orthogonal partial least squares discriminant analysis. Among the identified 114 phospholipid species in total, there were 11 hydroperoxides, 7 aldehydes, and 19 lysophospholipids found significantly elevated along with the increasing blood glucose, which were known as oxidation or degradation products. Furthermore, lysophosphatidylcholine 20:5 and lysophosphatidylcholine 22:6 were assessed as potential biomarkers in diabetic zebrafish. The current work would not only help to gain further insights into diabetes, but also contribute to find new clinical parameters for the screening of the promising antioxidant agents for its therapies.

Oxidative Stress Linked Organ Lipid Hydroperoxidation and Dysregulation in Mouse Model of Nonalcoholic Steatohepatitis: Revealed by Lipidomic Profiling of Liver and Kidney

“…Moreover, in return, the accelerated generation of ROS worsened the oxidative degree to the body. Similar trends of the elevated ROS levels, along with the lipid oxidation, were demonstrated not only in the organs of NAFLD/NASH [46,47], but also of other metabolic syndromes, such as diabetes mellitus [16,48], hypertension [49,50], CKD [51,52], and atherosclerosis [53]. Furthermore, the deficiency of the physiological lipids, particularly PUFA, ethanolamine phospholipids, and CL, leads to biomembrane dysfunction-related disturbances, especially mitochondrial dysfunction, which could oppositely cause free radical production and lipid peroxidation [29,54].…”

“…In contrast, there was no such difference for the kidney (Normal, 1462.5 nmol/g; NASH, 1382.2 nmol/g). Taking consideration of the molecular composition, as Figure 2C shows, the total TG accumulation in the NASH liver was predominantly due to the accretion of the more saturated species, especially those with shorter carbon chain length (i.e., [44][45][46][47][48][49][50][51][52][53][54] and fewer double bonds (i.e., 0-4). Even for the longer chain (e.g., C60) TG species, the changing trends depended on double bonds: those with fewer double bonds increased, and those with more double bonds decreased.…”

Untargeted Lipidomic Analysis of Plasma from High-fat Diet-induced Obese Rats Using UHPLC–Linear Trap Quadrupole–Orbitrap MS

“…In clinical chemistry, blood-based lipid biomarkers for obesity are crucial for the diagnosis of the disease. Moreover advanced LC/MS techniques were widely applied for lipid biomarker discovery in various models 26,27 . In the present study, a rodent rat model was used, and rats were fed with ND and HFD (fat source: HF-L-lard) for 8 weeks.…”

Mass Spectrometry-Based Zebrafish Toxicometabolomics: A Review of Analytical and Data Quality Challenges

“…For zebrafish metabolomics studies, short-term exposure effects could be assessed in terms of hours (e.g., 2.5–4 h; as described in, e.g., TG 236 in embryos and TG 203 in adult fish) or medium- to long-term exposures in the larval period (e.g., 3–7 days) [ 15 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. For chronic exposure, test guidelines are available for larval fish up to 30 days (e.g., TG 210) and for adult fish up to 20 or 60 days (e.g., TGs 229 and 234), when individually dissected fish tissues (e.g., liver, brain, intestinal samples, gonads) or blood samples could be analyzed [ 25 , 26 , 27 ].…”