NASH treatment study (Ldlr-/- mice on Western diet treated with/without omega-3 fatty acids)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE215225 | GEO | 2022/10/13
REPOSITORIES: GEO
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Project description:Mice on a reference (RD) or western diet (WD)
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Project description:There is a gap in our understanding of the protective effect of the essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) on proliferative retinopathies. In retinopathy of prematurity (ROP), DHA supplementation alone may not reduce the risk for severe disease. We found that in mouse neonates with hyperglycemia-associated retinopathy (HAR) with impaired retinal vessel growth modeling Phase I ROP versus controls, there was a strong metabolic shift in almost all types of retinal neuronal cells identified with single-cell transcriptomics. Loss of adiponectin (Apn-/-), modeling low APN seen in premature infants, caused a ω-3 and ω-6 LCPUFA imbalance in HAR mouse retinas. Dietary intake of ω-3 vs ω-6 LCPUFA promoted retinal vessel growth, associated with increased APN levels and increased retinal APN receptor AdipoR1 gene expression. Interestingly, we found that ω-6 vs. ω-3 LCPUFA was essential in maintaining retinal metabolism and neuronal development. Our findings suggest that both ω-3 and ω-6 LCPUFA are essential in protecting against retinal neurovascular dysfunction in Phase I ROP model. Maintaining adequate ω-6 LCPUFA levels is required while supplementing ω-3 LCPUFA to prevent retinopathy.
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Project description:The omega-3 fatty acid docosahexaenoic acid (DHA) has potent anti-atherogenic properties but its mechanisms of action at the vascular level remain poorly explored. Knowing the broad range of molecular targets of omega-3 fatty acids, microarray analysis was used to open-mindedly evaluate the effects of DHA on aorta gene expression in LDLR-/- mice and better understand its local anti-atherogenic action . Mice were fed an atherogenic diet and received daily oral gavages with oils rich in oleic acid or DHA. Bioinformatics analysis of microarray data first identified inflammation and innate immunity as processes the most affected by DHA supplementation within aorta. More precisely, several down-regulated genes were associated with the inflammatory functions of macrophages (e.g. CCL5, CCR7), cell movement (e.g. ICAM-2, SELP, PECAM-1), and the major histocompatibility complex (e.g. HLA-DQA1, HLA-DRB1). Interestingly, the expression of several genes were identified as specifc biomarkers of macrophage polarization and their changes suggested a preferential orientation towards a M2 reparative phenotype. This observation was supported by the upstream regulator analysis highlighting the involvment of three main regulators of macrophage polarization, namely PPARM-NM-3 (z-score=2.367, p=1.50x10-13), INFM-NM-3 (z-score=-2.797, p=2.81x10-14) and NFM-NM-:B (z-score=2.360, p=6.32x10-9). Moreover, immunohistological analysis of aortic root revealed an increased abundance of Arg1 (+111%, p=0.01), a specific biomarker of M2 macrophage.The present study showed for the first time that DHA supplementation during atherogenesis is associated with protective modulation of inflammation and innate immunity pathways within aorta putatively through the orientation of plaque macrophages towards a M2 reparative phenotype. Mice (LDLR-/-) Aorta samples. 2 groups: Control (K), DHA (C). Biological replicates=8. Dye switch.
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Project description:Persistent skin inflammation and impaired resolution are the main contributors to psoriasis and associated cardiometabolic complications. Omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to exert beneficial effects on inflammatory response and lipid function. However, a specific role in psoriasis disease and accompanied pathological mechanisms are still a matter of debate. Here, we aimed to perform a direct comparison between EPA and DHA diet treatment for 12 weeks of psoriasis-like skin inflammation in the K14-Rac1V12 mouse model. By utilizing sensitive high throughput techniques, we targeted EPA- and DHA-derived specialized pro-resolving mediators (SPMs) and identified tightly connected signaling pathways by RNA sequencing. Treatment with experimental diets significantly decreased circulating pro-inflammatory cytokines and plasma lipids, altered psoriasis macrophages phenotype and affected genes of atherosclerosis related pathways. The superficial role of these changes was related to DHA treatment and included skin abundance in resolvin D5, protectin X and maresin 2. EPA treated mice expressed less pronounced effects but resulted in decreasing skin accumulation of prostaglandin E2 and thromboxane B2. These results indicate that altering psoriasis with the omega-3 FA might have clinical significance and DHA treatment should be considered over EPA in this specific population.
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Project description:The omega-3 long chain poly-unsaturated fatty acid (n-3 LCPUFA) docosahexaenoic acid (DHA) plays a central role in fetal and neonatal development in humans, in particular the development of the brain and nervous system, and this has led to numerous studies focussed on determining the effect of exposure to an increased supply of DHA on pregnancy and neonatal outcomes. The aim of this study was to determine the impact of treatment with a DHA-enriched fish-oil emulsion on fatty acid composition, proliferation rate and gene expression in human placental HTR8/SVneo cells in vitro.
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