Shake it off: exploring drivers and outcomes of autotomy in marine invertebrates.

Autotomy refers to self-amputation where the loss of a limb or organ is generally said to be (1) in response to stressful external stimuli; (2) voluntary and nervously mediated; (3) supported by adaptive features that increase efficiency and simultaneously mediate the cost; and (4) morphologically delineated by a predictable breakage plane. It is estimated that this phenomenon has evolved independently nine different times across the animal kingdom, appearing in many different taxa, including vertebrate and invertebrate as well as aquatic and terrestrial animals. Marine invertebrates use this behaviour in a diversity of manners that have yet to be globally reviewed and critically examined. Here, published data from marine invertebrate taxa were used to explore instances of injury as an evolutionary driver of autotomy. Findings suggest that phyla (e.g. Echinodermata and Arthropoda) possibly experiencing high rates of injury (tissue damage or loss) are more likely to be able to perform autotomy. Additionally, this review looks at various morphological, physiological and environmental conditions that have either driven the evolution or maintained the behaviour of autotomy in marine invertebrates. Finally, the use of autotomic abilities in the development of more sustainable and less ecologically invasive fisheries is explored.

A rare case of intra-ovarian oocyte maturation.

The intra-ovarian presence of ootids, i.e. female gametes that have completed meiosis, is considered exceptional in the animal kingdom. The present study explores the first such case to be reported in a sea cucumber (Echinodermata: Holothuroidea). In the overwhelming majority of animals, including holothuroids, oocytes (i.e. immature female gametes) that are developing in the ovary undergo a primary arrest at the prophase stage of meiosis, which may last from days to decades. In free-spawning taxa, this arrest is normally lifted only during or shortly before transit in the gonoduct, when gamete release (spawning) is imminent. However, oocytes of the holothuroid Chiridota laevis were discovered to have resumed the second meiotic division including the completion of germinal vesicle breakdown and polar-body expulsion inside the ovary, effectively reaching the ootid stage concomitantly with ovulation (i.e. escape from follicle cells) prior to spawning. The potential drivers and significance of this exceptionally rare case of full intra-ovarian oogenic maturation are discussed.

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery.

BACKGROUND: Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. RESULTS: Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB + SG) (41.7 ± 4.6 vs 28.2 ± 6.8%; p = 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR = 0.75; 95%CI = 0.51-0.91; p = 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r2 = 0.83; p = 1.4 × 10-6). CONCLUSIONS: Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity. Trial registration ClinicalTrials.gov NCT02390973.

Rainbow bodies: Revisiting the diversity of coelomocyte aggregates and their synthesis in echinoderms.

The innate immunity of echinoderms has been a research focus since the early twentieth century, consistently providing ever deeper knowledge of its complexity and evolutionary aspects. At its core are coelomocytes, which are diverse cells collectively known to respond in a variety of ways, including via movement, phagocytosis, and aggregation. However, features of cellular immunity have never been compared in echinoderms from phylogenetic and distributional perspectives, to provide insight into ecological and evolutionary patterns. The present study catalyzed and characterized the formation of coelomocyte aggregates in members of all five extant classes of echinoderms. The morphological characteristics of these aggregates (including their colour, shape, texture, size) were assessed, as well as the major cells composing them. Coelomocyte diversity (both as free and aggregated forms) was determined to be maximum in class Holothuroidea, followed by Echinoidea, with the other classes showing similar levels of diversity. The colours of coelomocyte aggregates appeared to be more closely linked to phylogeny (classes, orders) rather than geographic range, or external colour of the species themselves. Asteroids and ophiuroids displayed primarily light-coloured aggregates, from transparent to green; while holothuroids, echinoids and crinoids demonstrated more vivid variants, from red to deep purple. The kinetics of aggregate formation and expulsion were monitored in selected species, showing immediate cellular response to foreign particulate matter in the form of encapsulation and various methods of expulsion, including through the dermal papillae of asteroids and the anus (cloaca) of holothuroids. The findings support that coelomocyte aggregate formation is a conserved immune response across all five extant classes of echinoderms with variations in their cell catalysts, complexity, shape, colour, and size.

The sea cucumber genome provides insights into morphological evolution and visceral regeneration.

Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.

Age determination in echinoderms: first evidence of annual growth rings in holothuroids.

While age is fundamental in animal biology, forming the basis of critical concepts such as life-history strategies, longevity and population structures, measuring this variable in some taxa remains problematic. Such is the case of holothuroid echinoderms, which play key roles in marine benthic communities from the shore to the abyss, and which are extensively fished in many regions across the globe. Here, we present and validate a promising ageing technique using the cold-water species Psolus fabricii. The method involves the extraction of the oldest dermal plates (largest dorsal ossicles) to preserve their original pigments and structure. While plates initially appear to have a uniform texture, polishing and dying them reveals layered ring patterns. A study of laboratory-reared juveniles, from settlement to 40 months of age, confirmed that one layer is added annually, making plates both larger and thicker, and generating successive light and dark rings, the latter representing the transition (overlap) between two layers. Therefore, each pair of rings represents an annual growth band. Size-at-age data obtained using this method revealed that growth of P. fabricii is slow and that wild individuals collected at diving depths had reached an age of several decades.

Active buoyancy adjustment increases dispersal potential in benthic marine animals.

While the study of dispersal and connectivity in the ocean typically centres on pelagic species and planktonic larval stages of benthic species, the present work explores an overlooked locomotor means in post-settlement benthic stages that redefines their dispersal potential. Members of the echinoderm class Holothuroidea colonize a diversity of marine environments world-wide, where they play key ecological and economical roles, making their conservation a priority. Holothuroids are commonly called sea cucumbers or sea slugs to reflect their slow movements and are assumed to disperse chiefly through pelagic larvae. The present study documents and explores their unexpected ability to actively modify their buoyancy, leading them to tumble or float at speeds orders of magnitudes faster than through benthic crawling. Two focal species representing different taxonomic orders, geographic distributions and reproductive strategies were studied over several years. Active buoyancy adjustment (ABA) was achieved through a rapid increase in water-to-flesh ratio by up to 740%, leading to bloating, and simultaneously detachment from the substrate. It occurred as early as 6 months post settlement in juveniles and was recorded in wild adult populations. In experimental trials, ABA was triggered by high conspecific density, decreasing salinity and increasing water turbidity. Based on field video footage, ABA-assisted movements generated speeds of up to 90 km/day. These findings imply that displacement during planktonic larval stages may not supersede the locomotor capacity of benthic stages, challenging the notion of sedentarity. Combining the present results and anecdotal reports, ABA emerges as a generalized means of dispersal among benthic animals, with critical implications for world-wide management and conservation of commercially and ecologically significant species.

Full allogeneic fusion of embryos in a holothuroid echinoderm.

Whole-body chimaeras (organisms composed of genetically distinct cells) have been directly observed in modular/colonial organisms (e.g. corals, sponges, ascidians); whereas in unitary deuterostosmes (including mammals) they have only been detected indirectly through molecular analysis. Here, we document for the first time the step-by-step development of whole-body chimaeras in the holothuroid Cucumaria frondosa, a unitary deuterostome belonging to the phylum Echinodermata. To the best of our knowledge, this is the most derived unitary metazoan in which direct investigation of zygote fusibility has been undertaken. Fusion occurred among hatched blastulae, never during earlier (unhatched) or later (larval) stages. The fully fused chimaeric propagules were two to five times larger than non-chimaeric embryos. Fusion was positively correlated with propagule density and facilitated by the natural tendency of early embryos to agglomerate. The discovery of natural chimaerism in a unitary deuterostome that possesses large externally fertilized eggs provides a framework to explore key aspects of evolutionary biology, histocompatibility and cell transplantation in biomedical research.

Influence of flow on locomotion, feeding behaviour and spatial distribution of a suspension-feeding sea cucumber.

Although movement in response to environmental conditions represents a fundamental link between animal behaviour and population ecology, it is rarely investigated in suspension feeders because they are generally perceived as sessile. Here, the interplay between water flow and fine locomotor and feeding behaviours was experimentally investigated for the first time in a free-moving suspension-feeding sea cucumber (Cucumaria frondosa; Echinodermata, Holothuroidea) using time-lapse videography in a mesocosm setting. Individuals moved away from static conditions in the weakest flow treatment and fled the strongest flows (>40 cm s-1) in the more dynamic treatments. The tentacles of individuals located in areas with flows of ≥40 cm s-1 was aligned with the direction of the current, whereas in flows <40 cm s-1, they were typically perpendicular to the direction of flow. Tentacle deployment and insertion rates (i.e. feeding rate) increased with flow, from 0.95 min-1 at 10 cm s-1 to 1.13 min-1 at 40 cm s-1 Three modes of locomotion were detected. Forward crawling was most frequent at flows ≤40 cm s-1, passive rolling dominated at flows >40 cm s-1 and active rolling occurred randomly at flows between 0 and 120 cm s-1 Overall, the flow regime favoured by C.frondosa was determined to be between 21 and 40 cm s-1, under which an optimal balance between efficient food capture and energy expenditure for attachment to the bottom was presumably found. These findings provide insight into the distribution and population dynamics of suspension-feeding holothuroids, and may also assist the fisheries management and aquaculture development of commercial species.

Markers of oil exposure in cold-water benthic environments: Insights and challenges from a study with echinoderms.

In spite of increasing naval activities and petroleum exploration in cold environments, there is currently a paucity of tools available to monitor oil contamination in boreal marine life, especially in sedentary (non-fish) species that dominate benthic communities. This research aimed to identify biotic sources of variation in biomarkers using subarctic echinoderms, and to identify suitable biomarkers of their exposure to hydrocarbons. The focal species included the sea star Asterias rubens, the brittle star Ophiopholis aculeata, the sea urchin Strongylocentrotus droebachiensis, and the sea cucumber Cucumaria frondosa, which are among the most abundant echinoderms in the North Atlantic and Arctic Oceans. The latter two species are also commercially exploited. A series of 96-h acute exposures of the water-accommodating fraction (WAF) of used lubricating oil (ULO) were performed in different seasons (i.e. distinct reproductive stages). Digestive and reproductive tissues were analyzed for baseline and response levels of glutathione peroxidase (GPx) and ethoxyresorufin-O-deethylase (EROD). GPx activity was detected in the pyloric caecum, stomach, and gonad of sea stars, the intestine and gonad of sea cucumbers, and the gonad of brittle stars and sea urchins. No seasonal variation in baseline GPx activity occurred. Upon exposure to the ULO WAF, sex-based differences were elicited in the GPx activity of sea star stomachs (lower in females than males). EROD activity was present in the pyloric caeca of sea stars, and the gonads of brittle stars and sea urchins. An interaction between season and sex on baseline EROD activity was measured in the gonads of sea urchins. Ovaries exhibited significant seasonal variation in EROD activity and had greater activity than testes during the spawning and post-spawning seasons. Seasonal variation in EROD activity also occurred in sea star pyloric caeca and brittle star gonads. Furthermore, testes of sea urchins exposed to the ULO WAF exhibited suppressed EROD activity compared to baseline levels. The nearly universal presence of GPx activity highlights its potential as a useful biomarker, while EROD activity was much more limited. Findings suggest a complex relationship between temporal and biotic factors on both the baseline and response levels of enzymatic activity, emphasizing the need to consider sex and sampling season in studies of biomarkers of hydrocarbon exposure in boreal indicator species that display annual reproductive cycles.

Factors Associated with the Intention of Registered Dietitians to Discuss Nutrigenetics with their Patients/Clients.

PURPOSE: The objective of this study was to investigate factors affecting the intention of Registered Dietitians (RDs) to discuss nutrigenetics with their patients/clients. METHODS: A survey based on the theory of planned behaviour (TPB; attitude, subjective norm, and perceived behavioural control) was developed and sent by email to RD members of the Ordre professionnel des diététistes du Québec. Multiple regression analyses were performed to examine the determinants of intention and behaviour. RESULTS: A total of 141 RDs completed the questionnaire (5.8% response rate). On a scale from -2 to 2 (from strongly disagree to strongly agree), the intention of discussing nutrigenetics with patients/clients was neutral (mean of -0.07 ± 0.92). The TPB construct of attitude was the most strongly associated with intention (ß = 0.66, P < 0.0001) followed by perceived behavioural control (ß = 0.33, P < 0.0001) and subjective norm (ß = 0.21, P = 0.03). Finally, 13 out of 141 RDs (~9%) actually practiced the behaviour, which was to have discussed nutrigenetics with their patients/clients in the last 3 months. Only perceived behavioural control contributed to explain the behaviour (ß = 0.17, P < 0.0001). CONCLUSIONS: Main determinants of the intention of RDs to discuss nutrigenetics with their patients/clients were determined. This knowledge will help inform the design of future educational content about nutrigenetics.

The cost of being valuable: predictors of extinction risk in marine invertebrates exploited as luxury seafood.

Extinction risk has been linked to biological and anthropogenic variables. Prediction of extinction risk in valuable fauna may not follow mainstream drivers when species are exploited for international markets. We use results from an International Union for Conservation of Nature Red List assessment of extinction risk in all 377 known species of sea cucumber within the order Aspidochirotida, many of which are exploited worldwide as luxury seafood for Asian markets. Extinction risk was primarily driven by high market value, compounded by accessibility and familiarity (well known) in the marketplace. Extinction risk in marine animals often relates closely to body size and small geographical range but our study shows a clear exception. Conservation must not lose sight of common species, especially those of high value. Greater human population density and poorer economies in the geographical ranges of endangered species illustrate that anthropogenic variables can also predict extinction risks in marine animals. Local-level regulatory measures must prevent opportunistic exploitation of high-value species. Trade agreements, for example CITES, may aid conservation but will depend on international technical support to low-income tropical countries. The high proportion of data deficient species also stresses a need for research on the ecology and population demographics of unglamorous invertebrates.

SREBF1 gene variations modulate insulin sensitivity in response to a fish oil supplementation.

BACKGROUND: An important inter-individual variability in the response of insulin sensitivity following a fish oil supplementation has been observed. The objective was to examine the associations between single nucleotide polymorphisms (SNPs) within sterol regulatory element binding transcription factor 1 (SREBF1) gene and the response of insulin sensitivity to a fish oil supplementation. METHODS: Participants (n = 210) were recruited in the greater Quebec City area and followed a 6-week fish oil supplementation protocol (5 g/day: 1.9-2.2 g EPA; 1.1 g DHA). Insulin sensitivity was assessed by the quantitative insulin sensitivity check index (QUICKI). Three tag SNPs (tSNPs) within SREBF1 gene were genotyped according to TAQMAN methodology. RESULTS: Three tSNPs (rs12953299, rs4925118 and rs4925115) covered 100% of the known genetic variability within SREBF1 gene. None of the three tSNPs was associated with either baseline fasting insulin concentrations (rs12953299, rs4925118 and rs4925115) (p = 0.29, p = 0.20 and p = 0.70, respectively) or QUICKI (p = 0.20, p = 0.18 and p = 0.76, respectively). The three tSNPs (rs12953299, rs4925118 and rs4925115) were associated with differences in the response of plasma insulin levels (p = 0.01, p = 0.005 and p = 0.004, respectively) and rs12953299 as well as rs4925115 were associated with the insulin sensitivity response (p = 0.009 and p = 0.01, respectively) to the fish oil supplementation, independently of the effects of age, sex and BMI. CONCLUSIONS: The genetic variability within SREBF1 gene has an impact on the insulin sensitivity in response to a fish oil supplementation. TRIAL REGISTRATION: clinicaltrials.gov: NCT01343342.

A new species of holothuroid from the Labrador Sea (eastern Canada): Pseudothyonelabradorensis sp. nov. (Echinodermata, Holothuroidea, Dendrochirotida, Sclerodactylidae).

A new species of holothuroid, Pseudothyonelabradorensis sp. nov. (order Dendrochirotida and family Sclerodactylidae), was discovered off the coast of Labrador (eastern Canada) at a depth of 740-969 m. Two specimens were described based on morphological and genetic parameters. Distinctive characters included pinkish body colour, presence of tube feet on a 'tail', supporting rod-shaped ossicles in the tube feet, and rod-shaped ossicles in the tentacles. To investigate its phylogenetic relationships, partial sequences of COI were obtained for the new species as well as for the type species P.raphanus and another North Atlantic species P.serrifera. According to the phylogenetic analysis, P.labradorensis sp. nov. appeared in a well-supported clade with P.raphanus and P.serrifera. Molecular data also suggest polyphyly of the genus, showing the Northeast Pacific species Pseudothyonebelli recovered outside of the clade containing the type species. Pseudothyonelabradorensis sp. nov. is the first species of the genus from the Northwest Atlantic. A key to the North Atlantic Pseudothyone is provided.

Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation.

Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption.

The metabolic signature associated with the Western dietary pattern: a cross-sectional study.

BACKGROUND: Metabolic profiles have been shown to be associated to obesity status and insulin sensitivity. Dietary intakes influence metabolic pathways and therefore, different dietary patterns may relate to modifications in metabolic signatures. The objective was to verify associations between dietary patterns and metabolic profiles composed of amino acids (AAs) and acylcarnitines (ACs). METHODS: 210 participants were recruited in the greater Quebec City area between September 2009 and December 2011. Dietary patterns had been previously derived using principal component analysis (PCA). The Prudent dietary pattern was characterised by higher intakes of vegetables, fruits, whole grain products, non-hydrogenated fat and lower intakes of refined grain products, whereas the Western dietary pattern was associated with higher intakes of refined grain products, desserts, sweets and processed meats. Targeted metabolites were quantified in 37 participants with the Biocrates Absolute IDQ p150 (Biocrates Life Sciences AG, Austria) mass spectrometry method (including 14 amino acids and 41 acylcarnitines). RESULTS: PCA analysis with metabolites including AAs and ACs revealed two main components explaining the most variance in overall data (13.8%). PC1 was composed mostly of medium- to long-chain ACs (C16:2, C14:2, C14:2-OH, C16, C14:1-OH, C14:1, C10:2, C5-DC/C6-OH, C12, C18:2, C10, C4:1-DC/C6, C8:1 and C2) whereas PC2 included certain AAs and short-chain ACs (xLeu, Met, Arg, Phe, Pro, Orn, His, C0, C3, C4 and C5). The Western dietary pattern correlated negatively with PC1 and positively with PC2 (r = -0.34, p = 0.05 and r = 0.38, p = 0.03, respectively), independently of age, sex and BMI. CONCLUSION: These findings suggest that the Western dietary pattern is associated with a specific metabolite signature characterized by increased levels of AAs including branched-chain AAs (BCAAs) and short-chain ACs.

Associations between dietary patterns and gene expression profiles of healthy men and women: a cross-sectional study.

BACKGROUND: Diet regulates gene expression profiles by several mechanisms. The objective of this study was to examine gene expression in relation with dietary patterns. METHODS: Two hundred and fifty four participants from the greater Quebec City metropolitan area were recruited. Two hundred and ten participants completed the study protocol. Dietary patterns were derived from a food frequency questionnaire (FFQ) by factor analysis. For 30 participants (in fasting state), RNA was extracted from peripheral blood mononuclear cells (PBMCs) and expression levels of 47,231 mRNA transcripts were assessed using the Illumina Human-6 v3 Expression BeadChips®. Microarray data was pre-processed with Flexarray software and analysed with Ingenuity Pathway Analysis (IPA). RESULTS: Two dietary patterns were identified. The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats. When individuals with high scores for the Prudent dietary pattern where compared to individuals with low scores, 2,083 transcripts were differentially expressed in men, 1,136 transcripts in women and 59 transcripts were overlapping in men and women. For the Western dietary pattern, 1,021 transcripts were differentially expressed in men with high versus low scores, 1,163 transcripts in women and 23 transcripts were overlapping in men and women. IPA reveals that genes differentially expressed for both patterns were present in networks related to the immune and/or inflammatory response, cancer and cardiovascular diseases. CONCLUSION: Gene expression profiles were different according to dietary patterns, which probably modulate the risk of chronic diseases. TRIAL REGISTRATION: NCT: NCT01343342.

Intra- and Interspecific Foraging and Feeding Interactions in Three Sea Stars and a Gastropod from the Deep Sea.

Competitive interactions come in a variety of forms and may be modulated by the size and number of individuals involved, and/or the resources available. Here, intra- and interspecific competitive behaviours for food (i.e., foraging/food search and feeding/food ingestion) were experimentally characterized and quantified in four co-existing deep-sea benthic species. Three sea stars (Ceramaster granularis, Hippasteria phrygiana, and Henricia lisa) and one gastropod (Buccinum scalariforme) from the bathyal Northwest Atlantic were investigated using video trials in darkened laboratory conditions. A range of competitive or cooperative behaviours occurred, depending on species (conspecific or heterospecific), comparative body size, and the number of individuals involved. Contrary to expectations, small individuals (or smaller species) were not always outcompeted by larger individuals (or larger species) when foraging and feeding. Moreover, faster species did not always outcompete slower ones while scavenging. Overall, this study sheds new light on scavenging strategies of co-existing deep-sea benthic species in food-limited bathyal environments, based on complex behavioural inter- and intraspecific relationships.

Circulating Human Metabolites Resulting from TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons from an Original Ex Vivo Clinical Trial.

TOTUM-070 is a patented polyphenol-rich blend of five different plant extracts showing separately a latent effect on lipid metabolism and potential synergistic properties. In this study, we investigated the health benefit of such a formula. Using a preclinical model of high fat diet, TOTUM-070 (3 g/kg of body weight) limited the HFD-induced hyperlipemia with a reduction in triglyceride (-32% after 6 weeks; -20.3% after 12 weeks) and non-HDL cholesterol levels (-21% after 6 weeks; -38.4% after 12 weeks). To further investigate such a benefit and its underlying mechanisms in humans, we designed an ex vivo clinical approach to collect the circulating bioactives resulting from TOTUM-070 ingestion and to determine their biological activities on human hepatocytes. Human serum was obtained from healthy subjects before and after intake of TOTUM-070 (4995 mg). The presence of circulating metabolites was assessed by UPLC-MS/MS. Serum containing metabolites was further incubated with hepatocytes cultured in a lipotoxic environment (palmitate, 250 µM). RNA sequencing analyses show that lipid metabolism was one of the most impacted processes. Using histologic, proteomic, and enzymatic assays, the effects of human TOTUM-070 bioactives on hepatocyte metabolism were characterized by (1) the inhibition of lipid storage, including both (2) triglycerides (-41%, p < 0.001) and (3) cholesterol (-50%, p < 0.001) intracellular content, (4) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity -44%, p < 0.001), and (5) a lowered fatty acid synthase protein level (p < 0.001). Altogether, these data support the beneficial impact of TOTUM-070 on lipid metabolism and provide new biochemical insights in human mechanisms occurring in liver cells.