Project description:Energy metabolism dysfunction is highly connected with aging. Aged mice could exhibit multiple energy metabolism disorders, such as insulin resistance, inhibition of fatty acid degradation and lipid accumulation. PPARα is a key transcriptional factor regulating genes of fatty acid β-oxidation, playing a crucial role in lipid metabolism and ATP production. However, the role of PPARα in retarding organ aging has not been fully elucidated. Herein, we investigated the beneficial effects of Omega-3 PUFAs, endogenous agonists of PPARα, in naturally aging mice, accelerated aging mice as well as several kinds of cells cultures. Moreover, we performed studies in mfat-1 transgenic mice at 24 months of age to explore the anti-aging effects of Omega-3 PUFAs. We found that Omega-3 PUFAs and fat-1 gene restored fatty acid β-oxidation and ATP production, reduced lipid accumulation, inhibited age-related pathological changes, preserved organ functions to delay aging process. Our results suggest Omega-3 PUFAs is a promising therapeutic approach to promote healthy aging in the elderly.
Project description:Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) have important signalling roles in the hypothalamus, a region of the brain that regulates whole-body energy homeostasis. While evidence suggests that high PUFA intake can impact hypothalamic activity, the underlying molecular mechanisms regulated by essential dietary PUFA (i.e., linoleic acid and alpha-linolenic acid) remain poorly described in this brain region. To differentiate the roles of essential dietary PUFA on hypothalamic function, we fed male rats high-fat diets (35% kcal/d) containing either safflower (linoleic acid) or flaxseed (alpha-linolenic acid) oil for 2 months. Control rats were fed a low-fat (16% kcal/d) diet containing soybean oil. Hypothalmic gene expression was investigated by microrray.
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status.
Project description:This study explored how the omega-6 to omega-3 fatty acid ratio in low-fish oil aquafeeds influences Atlantic salmon's antiviral and antibacterial immune responses. Atlantic salmon were fed aquafeeds rich in soy oil (high in omega-6) or linseed oil (high in omega-3) for 12 weeks and then challenged with bacterial (formalin-killed Aeromonas salmonicida; Asal) or viral-like (polyriboinosinic polyribocytidylic acid; pIC) antigens. The mRNA levels of 46 immune-relevant genes in the head kidneys of the salmon were analyzed via quantitative real-time polymerase chain reaction (RT-qPCR).
Project description:Insufficient energy intake to meet energy expenditure demands of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and Relative Energy Deficiency in Sport (REDs). REDs affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a better understanding of REDs and its treatment. To assess the molecular changes in response to energy deficiency, we implemented the ‘exercise-for-food’ paradigm, in which, food reward size is determined by wheel-running activity. By using this paradigm, we replicated several aspects of REDs in female and male mice, with high physical activity, and gradually reduced food intake, which results in weight loss, compromised bone health, organ-specific mass changes and altered rest-activity patterns. By integrating transcriptomics of 19 different organs, we provide a comprehensive dataset that will guide future understanding of REDs and may provide important implications for metabolic health and (athletic) performance.
Project description:Omega - 3 fatty acids of marine origin exert beneficial effects on lipid metabolism and can protect against insulin resistance in high fat diet (HFD)-fed animals. Simultaneously, recent studies showed that different lipid forms could have numerous consequences regarding the regulation of energy balance, nutrient absorption, and substrate metabolism. Indeed, when omega-3 was provided as triglycerides (TG, i.e. fish oil), it induced dose-dependently the expression of genes involved in lipid metabolism as well as fatty acid oxidation in small intestine of C57BL/6 mice fed various HFDs. As the underlying mechanism(s) explaining the differences in EPA/DHA bioavailability among various lipid forms of Omega-3 is not entirely clear, we performed a mouse study (n=8 per group) using purified HFDs with control HFD based on corn oil (cHF) and part of the lipids were replaced by omega-3 fish lipids in different forms: as either TG (cHF-F), marine phospholipids (PL; Krill oil, given at two different doses Krill-low (Krill-L) and Krill-high (Krill-H)), and as wax esters in the extract from the zooplankton Calanus finmarchicus (Calanus oil CAL-L representing same omega-3 levels as Krill-L diet). As a healthy control we fed a subset of mice standard chow (STD). All mice were fed their diet for 8 weeks and after sacrifice, whole small intestine was isolated, frozen and used for RNA isolation and microarray gene expression analysis using 8x60K Agilent arrays. Results showed that PL-H versus control cHFc induced specifically metabolic lipid pathways, while TG and PL-L mainly affected cytoskeleton regulation.
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.