Omega-3 from Flaxseed Oil Protects Obese Mice Against Diabetic Retinopathy Through GPR120 Receptor

Abstract

The chronic and low-grade inflammation induced by obesity seem to be the “first hit” to retinopathy associated to diabetes type 2. Herein, we hypothesized that omega-3 fatty acids from flaxseed oil enriched diet disrupt the pro-inflammatory status in the retina, protecting against retinopathy development. For eight weeks under a high-fat diet (HF), several physiological parameters were monitored to follow the metabolic homeostasis disruption. After this period, mice were treated with a HF substituted in part of lard by flaxseed oil (FS) for another eight weeks. Food behavior, weight gain, glucose and insulin sensitivity, electroretinography, RT-qPCR and western blots were carried out. The HF was able to induce a pro-inflammatory background in the retina, changing IL1β and TNFα. VEGF, a master piece of retinopathy, had early onset increased also induced by HF. The FS-diet was able to decrease inflammation and retinopathy and improved retinal electro stimuli compared to HF group. GPR120 and GPR40 (G Protein-Coupled Receptors 120 and 40), an omega-3 fatty acid receptors, were detected in the retina for the first time. FS-diet modulated the gene expression and protein content of these receptors. Thus, unsaturated fatty acids protect the retina from diabetes type 2 mice model from disease progression.

Calmodulin-binding transcription activator (CAMTA) genes family: Genome-wide survey and phylogenetic analysis in flax (Linum usitatissimum)

“…omega-3 fatty acids [39], which mitigate the inflammatory reactions and reduce the risk of cardiovascular diseases [40]. Moreover, other polyunsaturated fatty acids (PUFAs), present in flaxseeds, may protect the retina from harmful effects of diabetes mellitus type 2 [41]. Flaxseeds also possess lignans, which act as antioxidant due to their ability of scavenging free radicals [42].…”

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

“…Glaucoma, RP and DR [119][120][121][122] Spermidine Acts as a ROS scavenger by sequestering singlet oxygen and reactive species and reduced RGC death. Glaucoma [123] Lycopene Decreases NF-κB activation and ROS production in RPE cells, while increasing Nrf2 and GSH levels.…”

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

“…In another study, using a different mouse strain, the Swiss mice fed HFD for 8 weeks was shown to be sufficient to induce an increased body weight, increased fasting glucose, decreased insulin tolerance, and decreased OP (but without differences among amplitudes of wave a, b, or c, which are responsive for cones, rods, and epithelial cells, respectively). However, after 16 weeks, HFD induced a pro-inflammatory state in the retinal tissue (increased tumor necrosis factor (TNF)-α and interleukin 1 beta (IL-1β) gene expression and protein levels) and significantly increased levels of the inducer of VEGF that regulates angiogenesis by inducing proliferation of retinal endothelial cells and enhances vascular permeability [61]. A rodent model using HFD combined with STZ injection (single injection of high dose or multiple injections of low dose) to induce chronic hyperglycemia is the most widely accepted animal model for studying retinal complications in T2DM [8,62,64].…”