Project description:A moderate long-chain polyunsaturated fatty acids (LC-PUFAs) intake may improve obesity and metabolic disorders. However, regulating endogenous LC-PUFAs and their function is unclear. Here, adipocyte ILF3 expression promotes high-fat diet (HFD)–induced obesity and metabolic disorders by inhibiting endogenous omega-3 LC-PUFAs (n-3-LC-PUFA) biosynthesis. In patients with obesity, serum ILF3 levels are elevated and positively correlate with high triglyceride levels. The expression of ILF3 in adipose tissue from patients with obesity and HFD-induced obese mouse models is positively correlated with adipocyte size. Adipose tissue ILF3 expression in patients with obesity and HFD–induced obese mice positively correlates with adipocyte size. Adipocyte ILF3 deficiency significantly increases white adipose tissue browning, promotes brown adipose tissue thermogenesis, and improves HFD–induced obesity and metabolic disorders. ILF3 recruits DNMT1, which reduces FADS2 transcription and inhibits n-3-LC-PUFA biosynthesis. Similarly, sc26196, a FADS2-specific inhibitor, exacerbates obesity and metabolic disorders. Fenofibrate, an anti-triglyceride drug, improves obesity and metabolic disorders by inhibiting ILF3 expression and increasing endogenous n-3-LC-PUFA biosynthesis. Collectively, inhibiting adipocyte ILF3 expression may be an effective alternative treatment for these conditions.
Project description:The natural food for Atlantic salmon (Salmo salar) in freshwater has relatively lower levels of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) than found in prey for post-smolt salmon in seawater. Land-locked salmon such as the Gullspång population feed exclusively on freshwater type lipids during its entire life cycle, a successful adaptation derived from divergent evolution. Studying land-locked populations may provide insights into the molecular and genetic control mechanisms that determine and regulate n-3 LC-PUFA biosynthesis and retention in Atlantic salmon. A two factorial study was performed comparing land-locked and farmed salmon parr fed diets formulated with fish or rapeseed oil for 8 weeks. The land-locked parr had higher capacity to synthesise n-3 LC-PUFA as indicated by higher expression and activity of desaturase and elongase enzymes. The data suggested that the land-locked salmon had reduced sensitivity to dietary fatty acid composition and that dietary docosahexaenoic acid (DHA) did not appear to suppress expression of LC-PUFA biosynthetic genes or activity of the biosynthesis pathway, probably an evolutionary adaptation to a natural diet lower in DHA. Increased biosynthetic activity did not translate to enhanced n-3 LC-PUFA contents in the flesh and diet was the only factor affecting this parameter. Additionally, high lipogenic and glycolytic potentials were found in land-locked salmon, together with decreased lipolysis which in turn could indicate increased use of carbohydrates as an energy source and a sparing of lipid.
Project description:We studied genes that are related to atopic diseases [i.e., atopic eczema (AE)]. Immunological factors and principal genes involved in the biosynthesis of polyunsaturated fatty acids were included. We analyzed whether expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the expression of these genes.
Project description:In the model bryophyte Marchantia polymorpha, omega-3 (n3) polyunsaturated fatty acids (n3-PUFAs) and long-chain n3-PUFAs (n3-LCPUFAs) serve as precursors for bioactive jasmonates. However, how omega-3 fatty acid desaturases (n3-FADs) contribute to the production of n3-PUFAs and jasmonates remain unexplored. Here, we study the n3-FAD-dependent jasmonate signaling in the liverwort M. polymorpha. We found that MpFAD3, localized to the endoplasmic reticulum, prefers omega-6 (n6) arachidonic acid (ARA, 20:4n6) as the substrate thus controlling the biosynthesis of n3-LCPUFA derived jasmonates. Conversely, MpFAD7, found in the chloroplast, takes hexadecadienoic acid (HDA, 16:2n6) and linoleic acid (LA, 18:2n6) as substrates more efficiently and regulates the production of n3-PUFA derived jasmonates. Certain promiscuity was observed for these enzymes as evidenced by increased n6-(LC)PUFA levels in the doble Mpfad3fad7 mutant compared to single mutant lines individually. Mpfad7 and Mpfad3fad7 plants were more resistant to Fusarium oxysporum infection compared to wildtype control, suggesting a prominent role for n3-PUFA derived jasmonates in regulating defenses against necrotrophic pathogens. Remarkably, despite the lack of jasmonate-dependent anti-herbivore defenses in Mpfad3fad7 plants, Spodoptera exigua caterpillars performed equally badly on this double mutant and on wildtype plants, which states the dietary importance of essential n3-(LC)PUFAs for the caterpillar. Our results suggest that two conserved but specialized n3-FADs control n3-(LC)PUFA and jasmonate biosynthesis in Marchantia, and that food quality, namely the type and ratio of n3-(LC)PUFAs, contributes to insect performance in addition to jasmonate-dependent plant defenses.
Project description:Liver transcriptomes of Atlantic salmon families with contrasting flesh n-3 LC-PUFA profiles, and all fed the same 100% vegetable oil replacement diet, were compared by microarray analysis (Agilent oligoarray platform). The objective was to identify gene pathways and molecular mechanisms which might explain differences in flesh n-3 LC-PUFA content, independent of total lipid deposition, when salmon families are fed the same LC-PUFA deficient diet. A factorial design was chosen in which families containing higher and lower n-3 LC-PUFA relative levels were compared at similar total lipid percentages in flesh.
Project description:We studied genes that are related to atopic diseases [i.e., atopic eczema (AE)]. Immunological factors and principal genes involved in the biosynthesis of polyunsaturated fatty acids were included. We analyzed whether expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the expression of these genes. RT-PCR gene expression profile. The samples are described in the sumary. Each sample was measured in duplicate in the same TLDA card and we present the average of each sample.
Project description:Vegetable oils (VO) are possible substitutes for fish oil in aquafeeds but are limited by their lack of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). However, oilseed crops can be modified to produce n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, representing a potential option to fill the gap between supply and demand of these important nutrients. Camelina sativa was metabolically engineered to produce a seed oil with around 15 % total n-3 LC-PUFA to potentially substitute for fish oil in salmon feeds. Post-smolt Atlantic salmon (Salmo salar) were fed for 11-weeks with one of three experimental diets containing either fish oil (FO), wild-type Camelina oil (WCO) or transgenic Camelina oil (DCO) as added lipid source to evaluate fish performance, nutrient digestibility, tissue n-3 LC-PUFA, and metabolic impact determined by liver transcriptome analysis. The DCO diet did not affect any of the performance or health parameters studied and enhanced apparent digestibility of EPA and DHA compared to the WCO diet. The level of total n-3 LC-PUFA was higher in all the tissues of DCO-fed fish than in WCO-fed fish with levels in liver similar to those in fish fed FO. Endogenous LC-PUFA biosynthetic activity was observed in fish fed both the Camelina oil diets as indicated by the liver transcriptome and levels of intermediate metabolites such as docosapentaenoic acid, with data suggesting that the dietary combination of EPA and DHA inhibited desaturation and elongation activities. Expression of genes involved in phospholipid and triacylglycerol metabolism followed a similar pattern in fish fed DCO and WCO despite the difference in n-3 LC-PUFA contents.