Protective effects of fish oil on pre-diabetes: a lipidomic analysis of liver ceramides in rats

Abstract

A high intake of fat and sucrose can dramatically increase bioactive lipids such as ceramides in tissues. Ceramides regulate several steps in the insulin signal pathway. The effects of n-3 PUFA on insulin resistance are inconsistent, especially in liver. We investigated the effect of n-3 PUFA (EPA/DHA 1 : 1) from fish oil on hepatic ceramides in a pre-diabetic animal model. Three groups of rats were fed standard feed, high fat high sucrose feed (HFHS) or HFHS enriched with n-3 PUFA. We investigated by lipidomic analysis how supplementation of a HFHS diet with n-3 PUFA modifies the hepatic ceramide profile triggered by a HFHS diet. Our results show that n-3 PUFA modified the ceramide profile of the liver and reduced their total content in pre-diabetic rats. Significant linear correlations were observed between ceramides and biochemical insulin parameters. Long chain ceramide 18:1/18:0 showed a positive correlation with the HOMA index. Very long chain ceramide 18:1/24:0 showed a negative correlation with insulin and the HOMA index. Finally, very long chain ceramide 18:1/20:0 correlated negatively with glucose levels, plasmatic insulin levels and the HOMA index. In conclusion, the modulation of the ceramide profile in pre-diabetic rats may explain the protective action of n-3 PUFA against liver insulin resistance (IR) caused by an HFHS diet. We confirm the protective role of very long chain ceramide 18:1/24:0 and the harmful role of long chain ceramide 18:1/18:0 in the pre-diabetic state and propose ceramide 18:1/20:0 as a biomarker of early liver IR in rats.

Changes in liver proteins of rats fed standard and high-fat and sucrose diets induced by fish omega-3 PUFAs and their combination with grape polyphenols according to quantitative proteomics

“…FOM and FOM&GSE groups showed lower level of CSAD, involved in taurine biosynthesis from cysteine , which could indicate that glutathione synthesis was favoured in rats fed FOM diet rather than taurine synthesis, since cysteine is the limiting amino acid for both biosynthetic processes [52]. Accordingly, FOM groups tended to increase glutathione reduced levels [30]. Meanwhile, GSE diet down-regulated GLS2.…”

“…Adiposity index: ((total abdominal fat × 100)/body weight) and hepatosomatic index: ((liver weight × 100)/body weight) were also calculated. Plasma triglycerides, total cholesterol and insulin concentrations joint to the percentage of glycated hemoglobin (HbA1c) in blood were measured in the same animals by following protocols previously described [27][28][29] and the results are currently published [30,31] . In order to facilitate the reading of the present work, a summary of those are showed in the Supplementary Tables S1 and S2, which also provide the rest of biochemical measurements done.…”

“…According to proteomics design, comparisons among different supplements in the present research were made independently inside STD or HFHS backgrounds. The physiological effects of STD and HFHS, with or without supplements, were deeply discussed in the references [30] and [31].…”

Modulation of the Liver Protein Carbonylome by the Combined Effect of Marine Omega-3 PUFAs and Grape Polyphenols Supplementation in Rats Fed an Obesogenic High Fat and High Sucrose Diet

“…These parameters have already been studied in the same cohort of animals and partially published [15,22,23]. Rats fed the HFHS control diet developed a prediabetic state characterized by hyperinsulinemia and excess of visceral fat [13,19]. Results indicated that none of the supplementations influenced weight increase as well as adiposity and hepatosomatic indexes.…”

Breast Milk Lipidome Is Associated with Early Growth Trajectory in Preterm Infants

“…In adults, medium-and long-chain ceramides were found to enhance insulin sensitivity and 14 improve glucose homeostasis [70,71]. Such an impact has not been yet explored in infants.…”