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The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA) system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC–MS and MS/MS). One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG), digalactosyl diacylglyceride (DGDG), sulfoquinovosyl monoacylglyceride (SQMG), sulfoquinovosyl diacylglyceride (SQDG), the phospholipids phosphatidylcholine (PC), lyso-PC, phosphatidylglycerol (PG), lyso-PG, phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatic acid (PA), inositolphosphoceramide (IPC), and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS). Antiproliferative and anti-inflammatory effects promoted by lipid extract of Gracilaria sp. were evaluated by monitoring cell viability in human cancer lines and by using murine macrophages, respectively. The lipid extract decreased cell viability of human T-47D breast cancer cells and of 5637 human bladder cancer cells (estimated half-maximal inhibitory concentration (IC50) of 12.2 μg/mL and 12.9 μg/mL, respectively) and inhibited the production of nitric oxide (NO) evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) on the macrophage cell line RAW 264.7 (35% inhibition at a concentration of 100 μg/mL). These findings contribute to increase the ranking in the value-chain of Gracilaria sp. biomass cultivated under controlled conditions on IMTA systems.

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31Ulva species, green macroalgae, are widely distributed in the water across the globe, 32 being one of the most heavily-traded edible seaweeds. Nonetheless, although this genus 33 has been largely used in scientific studies, its lipidome remains rather unexplored. The 34 present study sheds light over the lipid profile of Ulva rigida produced in a land-based 35 integrated multi-trophic aquaculture (IMTA) system using liquid chromatography 36 coupled to high resolution mass spectrometry for molecular lipid species identification. 37The lipidome of U. rigida revealed the presence of distinct beneficial n-3 fatty acids for 38 human health, namely alpha-linoleic acid (ALA) and docosapentaenoic acid (DPA). A 39 total of 87 molecular species of glycolipids, 58 molecular species of betaine lipids and 57 40 molecular species of phospholipids were identified in the lipidome of U. rigida including 41 some species bearing PUFA and with described bioactive properties. Overall, the present 42 study contributes to the valorization and quality validation of sustainably farmed U. 43 rigida. 44 45 46 47 48 49 50 51 52 Edible macroalgae are a good source of beneficial compounds for human health that 53 display distinct functional properties that stimulate interest to number of high-value 54 chains (e.g., medical, nutraceutical and cosmeceutical) (Holdt and Kraan 2011; Leal et al. 55 2013; Abreu et al. 2014; Rajauria 2015; Roohinejad et al. 2016). Ulva spp. have long 56 been listed in FAO as one of the main macroalgae for commercial use (Naylor 1976). 57 These popular green seaweeds can be used fresh, dried, or in liquid extracts, either for 58 direct or processed consumption worldwide (McHugh 2003; Barriga et al. 2017). 59 Popularly known in the human food market as sea lettuce, Ulva spp. belongs to class 60 Ulvophyceae and can be found in marine and brackish waters, being widely distributed 61 across the globe. Ulva species are well adapted to aquaculture production and can be 62 successfully cultured by using an integrated multi-trophic aquaculture (IMTA) 63 framework (Bolton et al. 2008; Msuya and Neori 2008; Marinho et al. 2013; Shpigel et 64 al. 2017). This innovative and sustainable culture approach mimics the natural ecosystem 65 of species from different trophic levels, associating the production of fed species (e.g. 66 finfish) with other extractive organisms, namely marine invertebrates and/or algae, that 67 incorporate organic and inorganic compounds resulting from the metabolism of fed 68 species, as well as from uneaten feed. Overall, IMTA promotes a balanced production 69 framework that is environmentally sustainable and viable from an economic point of view 70 (Barrington et al. 2009; Chopin et al. 2012). The culture of seaweeds under an IMTA 71 approach allows the removal of excess nutrients, namely phosphorus and nitrogen, from 72 wastewater (Neori 2009; Lawton et al. 2013), while enhancing quality and stability of 73 seaweeds biomass and their biochemical profile (Abreu et al. 2014). 74Ulva species are con...

Brain mitochondria are fundamental to maintaining healthy functional brains, and their dysfunction is involved in age-related neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we conducted a research on how both non-synaptic and synaptic mitochondrial functions are compromised at an early stage of AD-like pathologies and their correlation with putative changes on membranes lipid profile, using 3 month-old nontransgenic and 3xTg-AD mice, a murine model of experimental AD. Bioenergetic dysfunction in 3xTg-AD brains is evidenced by a decrease of brain ATP levels resulting, essentially, from synaptic mitochondria functionality disruption as indicated by declined respiratory control ratio associated with a 50% decreased complex I activity. Lipidomics studies revealed that synaptic bioenergetic deficit of 3xTg-AD brains is accompanied by alterations in the phospholipid composition of synaptic mitochondrial membranes, detected either in phospholipid class distribution or in the phospholipids molecular profile. Globally, diacyl- and lyso-phosphatidylcholine lipids increase while ethanolamine plasmalogens and cardiolipins content drops in relation to nontransgenic background. However, the main lipidomic mark of 3xTg-AD brains is that cardiolipin cluster-organized profile is lost in synaptic mitochondria due to a decline of the most representative molecular species. In contrast to synaptic mitochondria, results support the idea that non-synaptic mitochondria function is preserved at the age of 3 months. Although the genetically construed 3xTg-AD mouse model does not represent the most prevalent form of AD in humans, the present study provides insights into the earliest biochemical events in AD brain, connecting specific lipidomic changes with synaptic bioenergetic deficit that may contribute to the progressive synapses loss and the neurodegenerative process that characterizes AD.