Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats

Abstract

Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.

Combined Intake of Fish Oil and D-Fagomine Prevents High-Fat High-Sucrose Diet-Induced Prediabetes by Modulating Lipotoxicity and Protein Carbonylation in the Kidney

“…These biometric determinations were concomitant with a statistically significant increase in plasma insulin and glucose, lower concentration of total cholesterol and HDL-Cholesterol (HDL-C), and higher percentage of fat in plasma. HFHS-diet intake provoked the ectopic accumulation of fat in erythrocytes, liver, and skeletal muscle, as previously described [ 43 ]. HFHS feeding elevated the levels of urea in plasma as well.…”

“…The complete description of diets is shown in Supplementary Table S1 . The fatty acid composition of the different diets is shown in Supplementary Table S2 and is the same used for research by Dasilva et al [ 43 ].…”

Influence of Dietary Inulin on Fecal Microbiota, Cardiometabolic Risk Factors, Eicosanoids, and Oxidative Stress in Rats Fed a High-Fat Diet

“…The HF diet provides lower amounts of n6 polyunsaturated fatty acids but higher amounts of saturated fatty acids than the STD diet. Differences in the incorporation of lipids were evidenced in previous studies by a reduced amount of polyunsaturated fatty acids and increased amount of saturated fatty acids in adipose tissue [ 68 ] and liver [ 69 ] samples after receiving the HF diet. However, a similar experimental model (strain, gender, initial age, initial body weight, diet) showed increased plasma IL-6 after 10 weeks on the HF diet compared to those fed the STD diet and increased lobular inflammation in liver as well as increased IL-6 and PGE2 in plasma after week 24 [ 5 , 70 ].…”

Effects of fish oil-containing nutrition supplementation in adult sepsis patients: a systematic review and meta-analysis

“…Fish oil, as the major source of omega-3 fatty acids, EPA and DHA, has been widely reported for its inflammatory mediation in cells, animal models and humans by curbing the production of the pro-inflammatory regulators, IL-6, IL-1β,TNF-α, IL-2, LTB4, PGE2, etc. [ 53 , 54 ]. EPA and DHA produce resolvins and DHA also gives rise to maresins and neuroprotectins through cyclooxygenase/LOX pathways [ 55 ].…”