Lipid Storage Research Articles

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called “athlete’s paradox”. In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY)

PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 Mb tandem duplication of chromosome 17 harbouring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves. To obtain better insights into the underlying pathogenic mechanisms in CMT1A, we investigated the role of PMP22 duplication in cellular homeostasis in CMT1A mouse models and in patient-derived induced pluripotent stem cells differentiated into Schwann cell precursors (iPSC-SCPs). We performed lipidomic profiling and bulk RNA sequencing (RNA-seq) on sciatic nerves of two developing CMT1A mouse models and on CMT1A patient-derived iPSC-SCPs. For the sciatic nerves of the CMT1A mice, cholesterol and lipid metabolism was downregulated in a dose-dependent manner throughout development. For the CMT1A iPSC-SCPs, transcriptional analysis unveiled a strong suppression of genes related to autophagy and lipid metabolism. Gene ontology enrichment analysis identified disturbances in pathways related to plasma membrane components and cell receptor signalling. Lipidomic analysis confirmed the severe dysregulation in plasma membrane lipids, particularly sphingolipids, in CMT1A iPSC-SCPs. Furthermore, we identified reduced lipid raft dynamics, disturbed plasma membrane fluidity and impaired cholesterol incorporation and storage, all of which could result from altered lipid storage homeostasis in the patient-derived CMT1A iPSC-SCPs. Importantly, this phenotype could be rescued by stimulating autophagy and lipolysis. We conclude that PMP22 duplication disturbs intracellular lipid storage and leads to a more disordered plasma membrane owing to an alteration in the lipid composition, which might ultimately lead to impaired axo-glial interactions. Moreover, targeting lipid handling and metabolism could hold promise for the treatment of patients with CMT1A.

Comparative analysis of the molecular starvation response of Southern Ocean copepods.

Large lipid-storing copepods dominate mesozooplankton biomass in the polar oceans and form a critical link between primary production and higher trophic levels. The ecological success of these species depends on their ability to survive periods of food deprivation in a highly seasonal environment, but the molecular changes that mediate starvation tolerance in these taxa are unknown. We conducted starvation experiments for two dominant Southern Ocean copepods, Calanoides acutus and Calanus propinquus, allowing us to compare the molecular starvation response between species. These species differ in life history, diet and metabolic traits, and expressed overlapping but distinct transcriptomic responses to starvation. Most starvation-response genes were species-specific, but we identified a conserved core set of starvation-response genes related to RNA and protein metabolism. We used phylotranscriptomics to place these results in the context of copepod evolution and found that starvation-response genes are under strong purifying selection at the sequence level and stabilizing selection at the expression level, consistent with their role in mediating essential biological functions. Selection on starvation-response genes was especially strong in our focal lipid-storing lineage relative to other copepod taxa, underscoring the significance of starvation tolerance for these species. We also found that certain key lipid enzymes (elongases and desaturases) have experienced diversification and positive selection in lipid-storing lineages, reflecting the unique lipid storage needs of these animals. Our results shed light on the molecular adaptations of high-latitude zooplankton to variable food conditions and suggest that starvation-response genes are under particularly strong sequence and expression constraints.

Fat-associated lymphoid clusters: Supporting visceral adipose tissue B cell function in immunity and metabolism.

It is now widely understood that visceral adipose tissue (VAT) is a highly active and dynamic organ, with many functions beyond lipid accumulation and storage. In this review, we discuss the immunological role of this tissue, underpinned by the presence of fat-associated lymphoid clusters (FALCs). FALC's distinctive structure and stromal cell composition support a very different immune cell mix to that found in classical secondary lymphoid organs, which underlies their unique functions of filtration, surveillance, innate-like immune responses, and adaptive immunity within the serous cavities. FALCs are important B cell hubs providing B1 cell-mediated frontline protection against infection and supporting B2 cell-adaptative immune responses. Beyond these beneficial immune responses orchestrated by FALCs, immune cells within VAT play important homeostatic role. Dysregulation of immune cells during obesity and aging leads to chronic pathological "metabolic inflammation", which contributes to the development of cardiometabolic diseases. Here, we examine the emerging and complex functions of B cells in VAT homeostasis and the metabolic complications of obesity, highlighting the potential role that FALCs play and emphasize the areas where further research is needed.

Effect of temporal thermal stress on Penaeus vannamei: Growth performance and physiological plasticity.

The present study evaluated the effect of temporal periods of hypothermia and hyperthermia, followed by an optimal temperature recovery phase on the growth, survival, and physiological response of Penaeus vannamei. Post-larvae were exposed to stress periods for 7 and 14 days at 22 °C and 32 °C each, followed by a recovery phase at 28 °C to complete seven experimental weeks, and were compared with a control group maintained at 28 °C. Weight gain, specific growth rate, feed intake, feed conversion ratio, and survival were weekly determined. Muscle, hepatopancreas, and hemolymph were sampled on the 14th day of the recovery phase for biochemical composition, and antioxidant and digestive enzyme activities determination. The shrimp presented a higher growth rate during short-term hyperthermia in contrast to shrimp under hypothermia that presented compensatory growth after thermal stress when the temperature was restored at 28 °C. Hyperthermia increased 12–13% the feed intake while this was diminished 21–29% by the hypothermia periods. Shrimp undergo metabolic adjustments following thermal stress, with short hypothermia increasing the lipase activity and lipid storage in the hepatopancreas, while short hyperthermia also enhances chymotrypsin activity and leads to higher protein and lipid accumulation. Conversely, prolonged hyperthermia induces greater energy consumption, depleting lipid and glycogen stores, while hypothermia causes scarce mobilization of energy reserves during recovery phase. Antioxidant enzyme activities were not affected by short-thermal stress (7d), while prolonged thermal stress (14d) significantly affected SOD, CAT, and GPx activities. The present study provides important insights into the physiological plasticity of P. vannamei during recovery from thermal stress.

Seasonal abundance, lipid storage, and energy density of Calanus finmarchicus and other copepod preyfields along the Northwest Atlantic continental shelf

Abstract Calanus finmarchicus is an abundant calanoid copepod in the New York Bight (NYB) that has energy-dense lipid stores. This study measured C. finmarchicus abundance, lipid storage and energy density and compared it to two other abundant calanoid species in the region. We compared the NYB C. finmarchicus preyfield characteristics with data from two other NW Atlantic coastal ecosystems, the Gulf of Maine (GoM) and Cape Cod Bay (CCB). Copepods from net tows were identified, enumerated, photographed and measured. These data were used to calculate animal biovolume and lipid content as well as the volumetric energy density of the copepod preyfield. C. finmarchicus were most abundant in spring and summer and the mean lipid storage of C. finmarchicus remained largely constant regardless of season and location within the NYB. Centropages typicus were abundant enough in the winter to be more energy-rich than C. finmarchicus. Temora longicornis, while also abundant, never surpassed the energy density of C. finmarchicus. C. finmarchicus in the NYB were comparably lipid-rich to those from the GoM and CCB. C. finmarchicus in the NYB can be a reliable energy source for local predators due to their high spring and summer abundances and year-round storage of high-energy wax esters.

Trophic interactions between common minke whales (Balaenoptera acutorostrata) and their prey during summer in the northern Barents Sea

Global warming is causing rapid change in marine food webs, particularly at northern latitudes where temperatures are increasing most rapidly. In this study, the diet of common minke whales Balaenoptera acutorostrata was assessed both in terms of short-term (morphological analyses of digestive tract contents) and longer-term (tissue chemical markers: fatty acids and stable isotopes) prey use in the northern Barents Sea to see if they are prey shifting. Samples (blubber cores, muscle, and stomach contents) were obtained from 158 common minke whales taken during Norwegian commercial whaling operations during summer over the period 2016–2020. Two prey items, capelin Mallotus villosus and krill (primarily Thysanoessa sp.), dominated the stomach contents in the entire period of investigation, which included sampling both in June and in August, similar to findings from earlier studies. A few gadoids were also observed in the whale stomachs. Lower blubber fatty acid (FA) contents in 2016/2017 as compared with 2018/2019 were observed. This is most likely explained by differences in sampling time (June in 2016/2017 vs August in 2018/2019, i.e., after a longer feeding period during the summer in the latter case). This explanation also fits with the fact that FA profiles of the 2018/2019 whales were more similar to the FA profiles of the potential prey, presumably reflecting the two months longer assimilation time for these whales. Multidimensional mixing models based on carbon and nitrogen isotope composition of the most likely prey groups suggested that the whales ate mostly krill in four of the five sampling years. In 2018 there were indications of a higher proportion of gadoid fish, showing some dietary flexibility. The trophic level of the whales’ feeding, as interpreted from the nitrogen isotope values, was positively correlated with blubber thickness suggesting that fish-eaters tended to assimilate more energy than whales that focused more exclusively on lower trophic prey. The variation suggested by different dietary analyses methods − stomach contents, fatty acids, and stable isotopes – most likely reflects different turnover times, with muscle stable isotopes likely representing several months of dietary integration, while lipid stores are more dynamic and may represent weeks, and stomach contents represent feeding events during the last few hours. The change in diet of minke whales from small pelagic fishes (in the past) to a greater quantity of krill and demersal fish (seen in this study) suggests that the whales are responding to the ongoing borealization of the Barents Sea ecosystem.

Assessing the effects of cold storage regimes of North American Bombus Gynes

AbstractBumble bees are the primary commercial pollinators for greenhouse‐grown crops and managing them requires insight into the Bombus life cycle. However, some aspects of the life cycle are not fully understood. Once mated, adult Bombus gynes can be stored for a short term at a constant low temperature (CLT). However, survival rates for some species are low during CLT, particularly when storage periods exceed a month. To address this, we tested the hypothesis that Bombus gynes stored in a fluctuating thermal regime (FTR) have increased survival compared to gynes stored in CLT. Specifically, the FTR had a baseline temperature of 2°C, with a daily fluctuation to 20°C relative to the CLT of 2°C with no warming pulse. We tested the effects of FTR on gyne survival and post‐cold storage lipid content in three species used for commercial pollination in North America: B. vosnesenskii, B. huntii and B. impatiens. We further assessed how additional factors influence cold storage survival, including gyne body weight, body size and colony age. Survival responses varied among species. Bombus vosnesenskii and B. huntii had a lower survival rate in FTR compared to CLT, but B. impatiens gynes had a significantly higher survival rate in FTR. We did not observe significant effects of FTR on lipid stores for any species, but survival increased with an increasing initial weight prior to cold storage. Moreover, gynes produced later in the colony life cycle had lower body weight and decreased survival compared to early emerging gynes. Our study provides insight into how cold storage conditions interact with colony and gyne characteristics to influence captive overwintering survival. Our findings have economic applications for improving commercial rearing and efforts for conservation rearing of at‐risk Bombus species.

A versatile delivery vehicle for cellular oxygen and fuels or metabolic sensor? A review and perspective on the functions of myoglobin.

A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O2) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O2 partial pressure (Po2) drops and Mb off-loads O2. Besides O2 storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR), and "ectopic" expression in some types of cancer cells and in brown adipose tissue (BAT). Data from Mb knockout (Mb-/-) mice and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools, modulation of BAT bioenergetics, thermogenesis, and lipid storage phenotypes. From these and other findings in the literature over many decades, Mb's function is not confined to delivering O2 in support of oxidative phosphorylation but may serve as an O2 sensor that modulates intracellular Po2- and NO-responsive molecular signaling pathways. This paradigm reflects a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Here, we review historic and emerging views related to the physiological roles for Mb and present working models illustrating the possible importance of interactions between Mb, gases, and small-molecule metabolites in regulation of cell signaling and bioenergetics.

Regulation of Myocardial Lipid Accumulation in the Development of Obesity

Energy metabolism is important in the development of heart disease, which is the leading cause of death worldwide. The importance of energy metabolism in disease is becoming even more clear with the rise in obesity, metabolic diseases, and the recognition that they all fit together as with the recent offcial report of a new syndrome named Cardiovascular-Kidney-Metabolic (CKM) Syndrome. A complete understanding of myocardial lipid storage and subsequent utilization of lipids is essential to understanding the impact of these metabolic diseases in the heart and on the development of cardiac dysfunction and hypertrophy. In this study we investigate how the heart controls fuel storage by taking advantage of the impact of the transcription factor peroxisome proliferator activated receptor α (PPARα) on 1) fatty acid metabolism and lipid accumulation, 2) its key role in sex differences in cardiac hypertrophy which we previously reported, and 3) the regulation of lipid droplets. It is controversial whether a decline in myocardial PPARα mediates cardiac hypertrophy and whether it increases or reduces lipid accumulation. Using our tamoxifen inducible cardiac-specific PPARα knockout mouse (cPPAR−/−) we see less cardiac lipid accumulation in response to a 5 week high fat diet. Our data indicate that this difference in triglyceride levels is present in both males and females. Importantly, this is not driven by a difference in fatty acid supply to these hearts. Serum fatty acid levels are not lower in cPPAR−/− vs Control mice fed a high fat diet. Further, we have not observed a difference in high fat diet induced body weight gain between cPPAR−/− and Control mice. We have begun to examine how these differences in high fat diet-induced lipid accumulation correlate with cardiac hypertrophy by looking at heart weight normalized to tibia length. While we did not expect 5 weeks of a high fat diet to induce cardiac hypertrophy, it is possible that the difference in cardiac lipid storage in the cPPAR−/− hearts could impact this. This measurement did not indicate a difference in cardiac hypertrophy between high fat diet fed cPPAR−/− and Control mice. We are utilizing this mouse as a model to investigate the regulation of lipid droplets and the lipid droplet proteome. So far, our results are indicating that the regulation of lipid droplet proteins is not affected in a uniform manner. For example, our data is suggesting that the expression of different members of the perilipin family are affected in distinct ways. Overall, these data indicate that a reduction in cardiac PPARα protects against obesity induced cardiac lipid accumulation. Going forward, it will be interesting to see how these changes occur in relation to the lipid droplet proteome and whether any changes that occur differentially in males vs female may be involved in sex differences in cardiac hypertrophy. Better understanding these factors will be essential for the development of safe and effective future therapies for CKM syndrome and other cardiovascular diseases. ND-EPSCoR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Emerging functions of the mitochondria-ER-lipid droplet three-way junction in coordinating lipid transfer, metabolism, and storage in cells.

Over the past two decades, we have witnessed a growing appreciation for the importance of membrane contact sites (CS) in facilitating direct communication between organelles. CS are tiny regions where the membranes of two organelles meet but do not fuse and allow the transfer of metabolites between organelles, playing crucial roles in the coordination of cellular metabolic activities. The significant advancements in imaging techniques and molecular and cell biology research have revealed that CS are more complex than what originally thought, and as they are extremely dynamic, they can remodel their shape, composition, and functions in accordance with metabolic and environmental changes and can occur between more than two organelles. Here, we describe how recent studies led to the identification of a three-way mitochondria-ER-lipid droplet CS and discuss the emerging functions of these contacts in maintaining lipid storage, homeostasis, and balance. We also summarize the properties and functions of key protein components localized at the mitochondria-ER-lipid droplet interface, with a special focus on lipid transfer proteins. Understanding tripartite CS is essential for unraveling the complexities of inter-organelle communication and cooperation within cells.

Hippo–YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ–TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo–YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Myoglobin: A versatile age-old oxygen carrying hemoprotein and its emerging role in metabolite regulation in diverse tissues

Myoglobin (Mb) is an age-old heme containing cytoplasmic protein primarily expressed in heart and skeletal muscles, which is capable of rapid release of O2 during the periods of hypoxia or anoxia. The canonical view of the primary physiological function of Mb is that it is a tissue oxygen (O2) storage protein supporting mitochondrial oxidative phosphorylation especially as the tissue O2 partial pressure ( pO2) drops and Mb increasingly offloads O2. For the past 50 years, many investigators are constantly exploring wide-range of physiological functions and metabolic regulation activities of Mb. Advanced genetic engineering tools and molecular techniques revealed important new insights and provided additional functions of Mb. However, accumulating evidence indicates that this paradigm is too narrow, especially in light of recent findings supporting plausible functions for Mb in lipid traffcking and sequestration, binding of small molecules such as lactate (LAC), pyruvate (PYR), glucose (GLU), polyamines, and glutathione (GSH), and “ectopic” expression in some types of cancer cells. Data from Mb knockout mice (Mb−/−) and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools and modulation of thermogenic brown adipose tissue (BAT) bioenergetics and lipid storage phenotypes. From these and other findings in the literature over many decades, it may be contemplated that the primary role for Mb under most conditions for Mb besides delivering O2 in support of oxidative phosphorylation, but also serve as an O2-sensor that modulates intracellular O2- and NO-responsive molecular signaling pathways. This paradigm shift reflect a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Herein, we present historic and emerging views related to the physiological roles for Mb, and working models illustrating the possible importance of interactions between Mb, gases, and small molecule metabolites in regulation of cell signaling and bioenergetics. USDA-ARS project 6026-51000-010-06S, Sturgis Foundation Grant AWD00054750 and ACRI-ABI Investigator Initiated Grant Award GR037175-4450S ABI. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Maternal Exercise Improves Infant Mesenchymal Stem Cell Lipid Storage and Oxidation, and Decreases Infant Adiposity

Rates of pediatric obesity are continuously rising and are likely to translate into high incidence of metabolic disease later in life. Maternal exercise during pregnancy has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to a multitude of infant peripheral tissue (e.g., skeletal muscle) and remain involved in mature tissue repair and maintenance. Importantly, these cells preserve the phenotype of an offspring donor and represent a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC collected during a randomized controlled trial to investigate if maternal exercise, regardless of exercise mode, affects infant adiposity and fatty acid oxidation. Compared to control, we observed >160% higher neutral lipid content in Ex-MSCs (p<0.01). However, this finding was coupled with significantly higher complete fatty acid oxidation to CO2 and lower incomplete fat oxidation (ASM production) in Ex-MSCs (p≤0.05). Infants in the exercise group had significantly lower body fat percentage compared to same age infants of controls at one month of age (p≤0.05). There was no difference in lean body mass volume (p>0.05) or infant one-month BMI (p=0.069). Together, these data indicate that maternal exercise exposure in utero is still associated with decreased infant adiposity one month after birth. MSC lipid content was positively associated with maternal fitness and exercise volume (p<0.01) during pregnancy. Finally, an increase in average maternal exercise volume (MET*min/wk; r=-0.4, p≤0.05) and total gestational MET*min (r=-0.36, p≤0.05), but not VO2max (p=0.07) was associated with infant 1-month body fat percentage. Together, these data showcase the influence of maternal exercise exposure on improvements in cellular metabolism and at 1 month of age. Collectively, our data suggests that exposure to maternal exercise could contribute to lower adiposity in early infancy. This project was supported by the American Heart Association (18IPA34150006 to L.E.M.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The CD36 scavenger receptor Bez regulates lipid redistribution from fat body to ovaries in Drosophila.

Lipid distribution in an organism is mediated by the interplay between lipoprotein particles, lipoprotein receptors and class B scavenger receptors of the CD36 family. CD36 is a multifunctional protein mediating lipid uptake, mobilization and signaling at the plasma membrane and inside of the cell. The CD36 protein family has 14 members in Drosophila melanogaster, which allows for the differentiated analysis of their functions. Here, we unravel a role for the so far uncharacterized scavenger receptor Bez in lipid export from Drosophila adipocytes. Bez shares the lipid binding residue with CD36 and is expressed at the plasma membrane of the embryonic, larval and adult fat body. Bez loss of function lowers the organismal availability of storage lipids and blocks the maturation of egg chambers in ovaries. We demonstrate that Bez interacts with the APOB homolog Lipophorin at the plasma membrane of adipocytes and trace the Bez-dependent transfer of an alkyne-labeled fatty acid from adipocytes to Lipophorin. Our study demonstrates how lipids are distributed by scavenger receptor-lipoprotein interplay and contribute to the metabolic control of development.

Preliminary hazard assessment of a new nature-inspired antifouling (NIAF) agent

A recently synthesized aminated 3,4-dioxygenated xanthone (Xantifoul2) was found to have promising antifouling (AF) effects against the settlement of the macrofouler Mytilus galloprovincialis larvae. Preliminary assessment indicated that Xantifoul2 has reduced ecotoxicological impacts: e.g., being non-toxic to the marine crustacea Artemia salina (<10 % mortality at 50 μM) and showing low bioconcentration factor in marine organisms. In order to meet the EU Biocidal Product Regulation, a preliminary hazard assessment of this new nature-inspired antifouling (NIAF) agent was conducted in this work. Xantifoul2 did not affect the swimming ability of the planktonic crustacean Daphnia magna, the growth of the diatom Phaeodactylum tricornutum, and the cellular respiration of luminescent Gram-negative bacteria Vibrio fischeri, supporting the low toxicity towards several non-target marine species. Regarding human cytotoxicity, Xantifoul2 did not affect the cell viability of retinal human cells (hTERT-RPE-1) and lipidomic studies revealed depletion of lipids involved in cell death, membrane modeling, lipid storage, and oxidative stress only at a high concentration (10 μM). Accelerated degradation studies in water were conducted under simulated sunlight to allow the understanding of putative transformation products (TPs) that could be generated in the aquatic ecosystems. Both Xantifoul2 and photolytic-treated Xantifoul2 in the aqueous matrix were therefore evaluated on several nuclear receptors (NRs). The results of this preliminary hazard assessment of Xantifoul2, combined with the high degradation rates in water, provide strong evidence of the safety of this AF agent under the evaluated conditions, and provide the support for future validation studies before this compound can be introduced in the market.

Microalgae production in olive mill wastewater fractions and cattle digestate slurry: Bioremediation effects and suitability for energy and feed uses

The possibility of obtaining energy or nutritive streams and bioremediation as an add-on opens new perspectives for the massive culturing of microalgal biomass on waste waters generated by the agro-food sector. Ordinary revenue streams are fully preserved, or even boosted, if they are used in microalgal cultivation; however, the suitability of wastewaters depends on multiple nutritional and toxic factors. Here, the effect of modulating the Olive Mill Wastewater (OMW) and cattle digestate (CD) fraction in the formulation of a growth medium on biomass accumulation and productivity of selected biomass fractions and their relevance for biofuel and/or feed production were tested for the microalga Scenedesmus dimorphus and for the cyanobacterium Arthrospira platensis (Spirulina). Tests highlighted the strong S. dimorphus adaptability to digestate, as on OMW, compared to A. platensis, with the maximum lipid storage (48 %) when culture medium was composed by 50 % of cattle digestate.

Limonoids isolated from Chisocheton ceramicusMiq. and the antiadipogenic mechanism of action of ceramicine B.

Different types of limonoids have been isolated from plants of the Chisocheton genus, notably from the species Chisocheton ceramicusMiq. which is largely distributed in the Indonesian archipelago and Malaysia region. A variety of natural products have been found in the bark of the tree and characterized as antimicrobial and/or antiproliferative agents. The isolated limonoids include chisomicines A-E, proceranolide, and a few other compounds. A focus is made on a large series of limonoids designated ceramicines Ato Z including derivatives with antiparasitic activities, antioxidant, antimelanogenic, and antiproliferative effectsand/or acting as regulators of lipogenesis. The lead compound in the series is ceramicine B functioning as a potent inhibitor of lipid droplet accumulation (LDA). Extracts from Chisocheton ceramicus and ceramicines have shown anti-LDA effects, with little or no cytotoxic effects. Ceramicine B is the most active compound functioning as a regulator of lipid storage in cells and tissues. Ceramicine B is a transcriptional repressor ofperoxisome proliferator-activated receptor γ (PPARγ) and an inhibitor of phosphorylation of the transcription factor FoxO1, acting via an upstream molecular target. Targeting of glycogen synthase kinase-3β is proposed, based on the analogy with structurally related limonoids known to target this enzyme, and supported by a molecular docking analysis. The target and pathway implicated in ceramicine B activity are discussed. The analysis shed light on ceramicine B as a natural product precursor for the design of novel compounds capable of reducing LDA in cells and of potential interest for the treatment of obesity, liver diseases, and other pathologies.

Identification of triacylglycerol remodeling mechanism to synthesize unusual fatty acid containing oils

Typical plant membranes and storage lipids are comprised of five common fatty acids yet over 450 unusual fatty acids accumulate in seed oils of various plant species. Plant oils are important human and animal nutrients, while some unusual fatty acids such as hydroxylated fatty acids (HFA) are used in the chemical industry (lubricants, paints, polymers, cosmetics, etc.). Most unusual fatty acids are extracted from non-agronomic crops leading to high production costs. Attempts to engineer HFA into crops are unsuccessful due to bottlenecks in the overlapping pathways of oil and membrane lipid synthesis where HFA are not compatible. Physaria fendleri naturally overcomes these bottlenecks through a triacylglycerol (TAG) remodeling mechanism where HFA are incorporated into TAG after initial synthesis. TAG remodeling involves a unique TAG lipase and two diacylglycerol acyltransferases (DGAT) that are selective for different stereochemical and acyl-containing species of diacylglycerol within a synthesis, partial degradation, and resynthesis cycle. The TAG lipase interacts with DGAT1, localizes to the endoplasmic reticulum (with the DGATs) and to puncta around the lipid droplet, likely forming a TAG remodeling metabolon near the lipid droplet-ER junction. Each characterized DGAT and TAG lipase can increase HFA accumulation in engineered seed oils.

β-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (Danio rerio) Model.

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. β-sitosterol is a natural product with significant hypolipidemic and cholesterol-lowering effects. However, the underlying mechanism of its action on aquatic products is not completely understood. A high-fat diet (HFD)-induced NAFLD zebrafish model was successfully established, and the anti-hyperlipidemic effect and potential mechanism of β-sitosterol were studied using oil red O staining, filipin staining, and lipid metabolomics. β-sitosterol significantly reduced the accumulation of triglyceride, glucose, and cholesterol in the zebrafish model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differential lipid molecules in β-sitosterol mainly regulated the lipid metabolism and signal transduction function of the zebrafish model. β-sitosterol mainly affected steroid biosynthesis and steroid hormone biosynthesis in the zebrafish model. Compared with the HFD group, the addition of 500 mg/100 g of β-sitosterol significantly inhibited the expression of Ppar-γ and Rxr-α in the zebrafish model by at least 50% and 25%, respectively. β-sitosterol can reduce lipid accumulation in the zebrafish model of NAFLD by regulating lipid metabolism and signal transduction and inhibiting adipogenesis and lipid storage.