Liver response to the consumption of fried sunflower oil.

Sunflower oil is one of the most commonly used fat sources in Argentina, and deep-fat frying is the popular food preparation process. The liver response of feeding a diet containing fried sunflower oil (SFOx) on growing rats was studied. Thirty-nine male weanling Wistar rats were randomly assigned to one of three diets for 8 wks: control (C), sunflower oil (SFO), and a diet containing SFOx, both of the sunflower diets were mixed with a commercial rat chow at weight ratio of 13% (w/w). Body weight and food consumption were recorded weekly. At t=8 wk, lipid profile and glycemia were measured. Visceral adiposity was registered. Liver was weighed and preserved for histological analysis, relative fatty acid profile, fibrosis markers and oxidative status. The three diets did not alter body weights; however, the SFOx fed rats showed increased energy intake and visceral fat; therefore, in liver saturated fat content, trans fatty acids, plus other unidentified minor components, such as hydroperoxides, hydroxides, epidioxides, hydroperoxy epidioxides, hydroxylepidioxides, and epoxides, were detected. The hepatosomatic index of SFOx rats was altered and showed hepatic steatosis. SFOx rats exhibited increased liver dichlorodihydrofluorescein-diacetate and thiobarbituric acid substance levels and oxidized-proteins content. Their livers had lower relative levels of monounsaturated, polyunsaturated fatty acids and catalase activity, but matrix metalloproteinase-9 activity was unchanged. Consumption of a diet rich in fried oil during growth could induce liver damage due to steatosis, excessive lipid toxicity and the accumulation of reactive oxygen species. Further progression could lead to hepatic fibrosis.

Neurolipidomics in schizophrenia: A not so well-oiled machine.

Most patients with schizophrenia (SCZ) do not exhibit violent behaviors and are more likely to be victims rather than perpetrators of violent acts. However, a subgroup of forensic detainees with SCZ exhibit tendencies to engage in criminal violations. Although numerous models have been proposed, ranging from substance use, serotonin transporter gene, and cognitive dysfunction, the molecular underpinnings of violence in SCZ patients remains elusive. Lithium and clozapine have established anti-aggression properties and recent studies have linked low cholesterol levels and ultraviolet (UV) radiation with human aggression, while vitamin D3 reduces violent behaviors. A recent study found that vitamin D3, omega-3 fatty acids, magnesium, and zinc lower aggression in forensic population. In this review article, we take a closer look at aryl hydrocarbon receptor (AhR) and the dysfunctional lipidome in neuronal membranes, with emphasis on cholesterol and vitamin D3 depletion, as sources of aggressive behavior. We also discuss modalities to increase the fluidity of neuronal double layer via membrane lipid replacement (MLR) and natural or synthetic compounds. This article is part of the Special Issue on "Personality Disorders".

A high-resolution 13C NMR approach for profiling fatty acid unsaturation in lipid extracts and in live Caenorhabditiselegans.

Unsaturated fatty acids (UFA) play a crucial role in central cellular processes in animals, including membrane function, development, and disease. Disruptions in UFA homeostasis can contribute to the onset of metabolic, cardiovascular, and neurodegenerative disorders. Consequently, there is a high demand for analytical techniques to study lipid compositions in live cells and multicellular organisms. Conventional analysis of UFA compositions in cells, tissues, and organisms involves solvent extraction procedures coupled with analytical techniques such as gas chromatography, MS and/or NMR spectroscopy. As a nondestructive and nontargeted technique, NMR spectroscopy is uniquely capable of characterizing the chemical profiling of living cells and multicellular organisms. Here, we use NMR spectroscopy to analyze Caenorhabditis elegans, enabling the determination of their lipid compositions and fatty acid unsaturation levels both in cell-free lipid extracts and in vivo. The NMR spectra of lipid extracts from WT and fat-3 mutant C. elegans strains revealed notable differences due to the absence of Δ-6 fatty acid desaturase activity, including the lack of arachidonic and eicosapentaenoic acyl chains. Uniform 13C-isotope labeling and high-resolution 2D solution-state NMR of live worms confirmed these findings, indicating that the signals originated from fast-tumbling lipid molecules within lipid droplets. Overall, this strategy permits the analysis of lipid storage in intact worms and has enough resolution and sensitivity to identify differences between WT and mutant animals with impaired fatty acid desaturation. Our results establish methodological benchmarks for future investigations of fatty acid regulation in live C. elegans using NMR.

Prevention of chemotherapy-related bone loss with doxorubicin-loaded solid lipid nanoparticles.

Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model.Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy.Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals.Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival.

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Groundnut and tree nuts: a comprehensive review on their lipid components, phytochemicals, and nutraceutical properties.

The health benefits of nut consumption have been extensively demonstrated in observational studies and intervention trials. Besides the high nutritional value, countless evidences show that incorporating nuts into the diet may contribute to health promotion and prevention of certain diseases. Such benefits have been mostly and certainly attributed not only to their richness in healthy lipids (plentiful in unsaturated fatty acids), but also to the presence of a vast array of phytochemicals, such as polar lipids, squalene, phytosterols, tocochromanols, and polyphenolic compounds. Thus, many nut chemical compounds apply well to the designation "nutraceuticals," a broad umbrella term used to describe any food component that, in addition to the basic nutritional value, can contribute extra health benefits. This contribution analyses the general chemical profile of groundnut and common tree nuts (almond, walnut, cashew, hazelnut, pistachio, macadamia, pecan), focusing on lipid components and phytochemicals, with a view on their bioactive properties. Relevant scientific literature linking consumption of nuts, and/or some of their components, with ameliorative and/or preventive effects on selected diseases - such as cancer, cardiovascular, metabolic, and neurodegenerative pathologies - was also reviewed. In addition, the bioactive properties were analyzed in the light of known mechanistic frameworks.

Clinicogenetic characterization of cerebrotendinous xanthomatosis in Brazil.

There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.

Nitrogen limitation-induced adaptive response and lipogenesis in the Antarctic yeast Rhodotorula mucilaginosa M94C9.

The extremotolerant red yeast Rhodotorula mucilaginosa displays resilience to diverse environmental stressors, including cold, osmolarity, salinity, and oligotrophic conditions. Particularly, this yeast exhibits a remarkable ability to accumulate lipids and carotenoids in response to stress conditions. However, research into lipid biosynthesis has been hampered by limited genetic tools and a scarcity of studies on adaptive responses to nutrient stressors stimulating lipogenesis. This study investigated the impact of nitrogen stress on the adaptive response in Antarctic yeast R. mucilaginosa M94C9. Varied nitrogen availability reveals a nitrogen-dependent modulation of biomass and lipid droplet production, accompanied by significant ultrastructural changes to withstand nitrogen starvation. In silico analysis identifies open reading frames of genes encoding key lipogenesis enzymes, including acetyl-CoA carboxylase (Acc1), fatty acid synthases 1 and 2 (Fas1/Fas2), and acyl-CoA diacylglycerol O-acyltransferase 1 (Dga1). Further investigation into the expression profiles of RmACC1, RmFAS1, RmFAS2, and RmDGA1 genes under nitrogen stress revealed that the prolonged up-regulation of the RmDGA1 gene is a molecular indicator of lipogenesis. Subsequent fatty acid profiling unveiled an accumulation of oleic and palmitic acids under nitrogen limitation during the stationary phase. This investigation enhances our understanding of nitrogen stress adaptation and lipid biosynthesis, offering valuable insights into R. mucilaginosa M94C9 for potential industrial applications in the future.

Rhythms in lipid droplet content driven by a metabolic oscillator are conserved throughout evolution.

The biological clock in eukaryotes controls daily rhythms in physiology and behavior. It displays a complex organization that involves the molecular transcriptional clock and the redox oscillator which may coordinately work to control cellular rhythms. The redox oscillator has emerged very early in evolution in adaptation to the environmental changes in O2 levels and has been shown to regulate daily rhythms in glycerolipid (GL) metabolism in different eukaryotic cells. GLs are key components of lipid droplets (LDs), intracellular storage organelles, present in all living organisms, and essential for energy and lipid homeostasis regulation and survival; however, the cell bioenergetics status is not constant across time and depends on energy demands. Thus, the formation and degradation of LDs may reflect a time-dependent process following energy requirements. This work investigated the presence of metabolic rhythms in LD content along evolution by studying prokaryotic and eukaryotic cells and organisms. We found sustained temporal oscillations in LD content in Pseudomonas aeruginosa bacteria and Caenorhabditis elegans synchronized by temperature cycles, in serum-shock synchronized human embryonic kidney cells (HEK 293 cells) and brain tumor cells (T98G and GL26) after a dexamethasone pulse. Moreover, in synchronized T98G cells, LD oscillations were altered by glycogen synthase kinase-3 (GSK-3) inhibition that affects the cytosolic activity of the metabolic oscillator or by knocking down LIPIN-1, a key GL synthesizing enzyme. Overall, our findings reveal the existence of metabolic oscillations in terms of LD content highly conserved across evolutionary scales notwithstanding variations in complexity, regulation, and cell organization.

The polyunsaturated fatty acid docosahexaenoic affects mitochondrial function in prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) shows a rewired metabolism featuring increased fatty acid uptake and synthesis via de novo lipogenesis, both sharply related to mitochondrial physiology. The docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that exerts its antitumoral properties via different mechanisms, but its specific action on mitochondria in PCa is not clear. Therefore, we investigated whether the DHA modulates mitochondrial function in PCa cell lines. METHODS: Here, we evaluated mitochondrial function of non-malignant PNT1A and the castration-resistant (CRPC) prostate 22Rv1 and PC3 cell lines in response to DHA incubation. For this purpose, we used Seahorse extracellular flux assay to assess mitochondria function, [14C]-glucose to evaluate its oxidation as well as its contribution to fatty acid synthesis, 1H-NMR for metabolite profile determination, MitoSOX for superoxide anion production, JC-1 for mitochondrial membrane polarization, mass spectrometry for determination of phosphatidylglycerol levels and composition, staining with MitoTracker dye to assess mitochondrial morphology under super-resolution in addition to Transmission Electron Microscopy, In-Cell ELISA for COX-I and SDH-A protein expression and flow cytometry (Annexin V and 7-AAD) for cell death estimation. RESULTS: In all cell lines DHA decreased basal respiratory activity, ATP production, and the spare capacity in mitochondria. Also, the omega-3 induced mitochondrial hyperpolarization, ROS overproduction and changes in membrane phosphatidylglycerol composition. In PNT1A, DHA led to mitochondrial fragmentation and it increased glycolysis while in cancer cells it stimulated glucose oxidation, but decreased de novo lipogenesis specifically in 22Rv1, indicating a metabolic shift. In all cell lines, DHA modulated several metabolites related to energy metabolism and it was incorporated in phosphatidylglycerol, a precursor of cardiolipin, increasing the unsaturation index in the mitochondrial membrane. Accordingly, DHA triggered cell death mainly in PNT1A and 22Rv1. CONCLUSION: In conclusion, mitochondrial metabolism is significantly affected by the PUFA supplementation to the point that cells are not able to proliferate or survive under DHA-enriched condition. Moreover, combination of DHA supplementation with inhibition of metabolism-related pathways, such as de novo lipogenesis, may be synergistic in castration-resistant prostate cancer.

The link between alterations in circadian rhythms and lipid metabolism in bipolar disorder: the lipid droplets hypothesis.

Bipolar disorder (BD) is a neuropsychiatric illness characterized by recurrent episodes of mania and depression, leading to profound cognitive and functional impairments, psychiatric and metabolic comorbidities, and substantial healthcare costs. Due to its complex nature and absence of specific biomarkers, BD presents significant daily challenges for clinicians. Therefore, advancing our understanding of BD pathophysiology is essential to identify novel diagnostic biomarkers and potential therapeutic targets. Although its neurobiology remains unclear, disruption of circadian rhythms and lipid alterations have emerged as key hallmarks of BD. As essential components of the brain, lipids play a pivotal role in regulating synaptic activity and neuronal development. Thus, alterations in brain lipids may contribute to the neuroanatomical changes and reduced neuroplasticity observed in BD. The levels of toxic lipids inside the cell are buffered by lipid droplets that regulate the storage of neutral lipids. These dynamic organelles adapt to cellular needs, and their dysregulated accumulation has been linked to various pathological conditions. Notably, lipid droplets and various lipid classes display rhythmic oscillations throughout the 24-hour cycle, suggesting a link between lipid metabolism, circadian rhythms and lipid droplets. In this review, we explore the impairment of circadian rhythms and lipid metabolism in BD, along with evidence demonstrating that circadian clocks regulate the accumulation of lipid droplets. Importantly, we propose the "lipid droplets hypothesis for BD" that considers that the compromised lipid metabolism in BD is intimately associated with alterations in the lipid droplets homeostasis, which can be driven by disturbances in the circadian clocks.

Unlocking Secrets: Lipid Metabolism and Lipid Droplet Crucial Roles in SARS-CoV-2 Infection and the Immune Response.

Lipid droplets (LD) are crucial for maintaining lipid and energy homeostasis within cells. LDs are highly dynamic organelles that present a phospholipid monolayer rich in neutral lipids. Additionally, LDs are associated with structural and non-structural proteins, rapidly mobilizing lipids for various biological processes. Lipids play a pivotal role during viral infection, participating during viral membrane fusion, viral replication, and assembly, endocytosis, and exocytosis. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection often induces LD accumulation, which is used as a source of energy for the replicative process. These findings suggest that LDs are a hallmark of viral infection, including SARS-CoV-2 infection. Moreover, LD participates in the inflammatory process and cell signaling, activating pathways related to innate immunity and cell death. Accumulating evidence demonstrates that LD induction by SARS-CoV-2 is a highly coordinated process, aiding replication and evading the immune system, and may contribute to the different cell death process observed in various studies. Nevertheless, recent research in the field of LDs suggests these organelles according to the pathogen and infection conditions may also play roles in immune and inflammatory responses, protecting the host against viral infection. Understanding how SARS-CoV-2 influences LD biogenesis is crucial for developing novel drugs or repurposing existing ones. By targeting host lipid metabolic pathways exploited by the virus, it is possible to impact viral replication and inflammatory responses. This review seeks to discuss and analyze the role of LDs during SARS-CoV-2 infection, specifically emphasizing their involvement in viral replication and the inflammatory response.

Novel lipid-interaction motifs within the C-terminal domain of Septin10 from Schistosoma mansoni.

Septins are cytoskeletal proteins and their interaction with membranes is crucial for their role in various cellular processes. Septins have polybasic regions (PB1 and PB2) which are important for lipid interaction. Earlier, we and others have highlighted the role of the septin C-terminal domain (CTD) to membrane interaction. However, detailed information on residues/group of residues important for such feature is lacking. In this study, we investigate the lipid-binding profile of Schistosoma mansoni Septin10 (SmSEPT10) using PIP strip and Langmuir monolayer adsorption assays. Our findings highlight the CTD as the primary domain responsible for lipid interaction in SmSEPT10, showing binding to phosphatidylinositol phosphates. SmSEPT10 CTD contains a conserved polybasic region (PB3) present in both animals and fungi septins, and a Lys (K367) within its putative amphipathic helix (AH) that we demonstrate as important for lipid binding. PB3 deletion or mutation of this Lys (K367A) strongly impairs lipid interaction. Remarkably, we observe that the AH within a construct lacking the final 43 amino acid residues is insufficient for lipid binding. Furthermore, we investigate the homocomplex formed by SmSEPT10 CTD in solution by cross-linking experiments, CD spectroscopy, SEC-MALS and SEC-SAXS. Taken together, our studies define the lipid-binding region in SmSEPT10 and offer insights into the molecular basis of septin-membrane binding. This information is particularly relevant for less-studied non-human septins, such as SmSEPT10.

Nutriomic Effects of Precision Lipids on Murine Hepatic Triacylglycerol Alterations Induced by High-Fat Diets.

INTRODUCTION: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. METHODS: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. RESULTS: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. CONCLUSION: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.

Metabolic dysfunction associated fatty liver disease in healthy weight individuals.

Metabolic dysfunction associated fatty liver disease (MAFLD) is an increasing public health problem, affecting one third of the global population. Contrary to conventional wisdom, MAFLD is not exclusive to obese or overweight individuals. Epidemiological studies have revealed a remarkable prevalence among healthy weight individuals, leading investigations into the genetic, lifestyle, and dietary factors that contribute to the development of MAFLD in this population. This shift in perspective requires reconsideration of preventive strategies, diagnostic criteria and therapeutic approaches tailored to address the unique characteristics of MAFLD healthy weight individuals. It also underscores the importance of widespread awareness and education, within the medical community and among the general population, to promote a more inclusive understanding of liver metabolic disorders. With this review, we aim to provide a comprehensive exploration of MAFLD in healthy weight individuals, encompassing epidemiological, pathophysiological, and clinical aspects.

Evaluation of the Antioxidant Activity and Phenolic Composition of Different Monofloral and Polyfloral Brazilian Honey Extracts.

This study aimed to evaluate the chemical composition and antioxidant activity of phenolic extracts from monofloral and polyfloral honey samples obtained from different Brazilian regions. The chemical composition (total content of phenolic compounds and flavonoids) of extracts were measured by using colorimetric assays and analyzed by high performance liquid chromatographic (HPLC-DAD). The antioxidant activity was evaluated by chemical and biochemical assays (reducing power assay, 1,1-diphenyl-2-picrylhydrazyl (DPPH⋅) and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic) acid (ABTS⋅+) scavenger assays. It was also investigated the ability of extracts in attenuate lipid peroxidation induced by Fe2+ in phospholipids. The obtained results clearly demonstrated that the botanical origin and geographical region of honey collection influenced the chemical composition and antioxidant activity of extracts. Furthermore, the samples were constituted by phenolic acids and flavonoids, which p-coumaric acid was predominant among the compounds identified. All samples were able to scavenge free radicals and inhibit lipid peroxidation, and good correlations were obtained between the flavonoid content and honey color. In conclusion, the obtained extracts were constituted by antioxidant compounds, which reinforce the usage of honey in human diets, and demonstrated that the region of honey collection strong influenced in the chemical composition and, consequently, its biological effect.

Very Low Calorie Ketogenic Diet: What Effects on Lipid Metabolism?

PURPOSE OF REVIEW: This review aims to critically examine how VLCKD affects plasma lipoprotein, lipid and cholesterol metabolism. Cardiovascular disease is a worldwide health problem affecting millions of people and leading to high rates of mortality and morbidity. There is a well-established association between cardiovascular disease and circulating cholesterol. Various dietary recommendations are currently available for the management of dyslipidemia. RECENT FINDINGS: The very low-calorie ketogenic diet (VLCKD) is becoming increasingly popular as a treatment option for several pathological conditions, including dyslipidemia. In addition to being low in calories, the VLCKD's main feature is its unique calorie distribution, emphasizing a reduction in carbohydrate consumption in favor of fat as the primary calorie source. Lowering calorie intake through a VLCKD can reduce the endogenous production of cholesterol. However, if the foods consumed are from animal sources, dietary cholesterol intake may increase due to the higher fat content of animal products. When combined, these dietary practices may have opposing effects on plasma cholesterol levels. Studies investigating the impact of VLCKD on plasma cholesterol and low-density lipoprotein cholesterol levels report contradictory findings. While some studies found an increase in low-density lipoprotein cholesterol levels, others showed a decrease in total cholesterol and low-density lipoprotein cholesterol, along with an increase in high-density lipoprotein cholesterol.

Fresh Carrier for an Old Topical Local Anesthetic: Benzocaine in Nanostructured Lipid Carriers.

Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

Bioaccessibility of condensed tannins and their effect on the physico-chemical characteristics of lamb meat.

The bioaccessibility of tannins as antioxidants in meat is essential to maximise their effectiveness in protecting the product. This property determines the amount of tannins available to interact with meat components, inhibiting lipid and protein oxidation and, consequently, prolonging shelf life and preserving the sensory quality of the product. The objective of this study was to evaluate the bioaccessibility of condensed tannins (CT) from Acacia mearnsii extract (AME) and their effect on the physico-chemical characteristics of fattened lamb meat. Thirty-six Dorset × Hampshire lambs (3 months old and 20.8 ± 3.3 kg live weight) were used. The lambs were distributed equally (n = 9) into four treatments: T1, T2, T3 and T4, which included a basal diet plus 0%, 0.25%, 0.5% and 0.75% of CT from AME, respectively. At the end of the fattening period, bioaccessibility was evaluated, the animals were slaughtered and a sample of the longissimus dorsi (LD) muscle was collected to assess colour, lipid oxidation, cooking weight loss and shear force on days 1, 4, 7 and 14 of shelf-life, in samples preserved at -20 °C. In addition, the long chain fatty acid profile was analysed. A completely randomised design was used, and the means were compared with Tukey's test (P < 0.05). The mean lightness (L*), yellowness (b*) and hue (H*) values were higher for T3 and T4. The addition of CT did not affect (P > 0.05) redness (a*), cooking weight loss (CWL) or shear force (SF). T4 decreased (P < 0.05) stearic acid and increased cis-9 trans-12 conjugated linoleic acid (CLA). Bioaccessibility was higher in the supplemented groups (T1 < T2, T3 and T4). In conclusion, supplementing CT from AME in the diet of lambs did not reduce lipid oxidation, but T3 or T4 improved some aspects of meat colour and CLA deposition.

Lipid Metabolism in Insect Vectors of Diseases.

According to the World Health Organization vector-borne diseases account for more than 17% of all infectious diseases, causing more than 700,000 deaths annually. Vectors are organisms that are able to transmit infectious pathogens between humans, or from animals to humans. Many of these vectors are hematophagous insects, which ingest the pathogen from an infected host during a blood meal, and later transmit it into a new host. Malaria, dengue, African trypanosomiasis, yellow fever, leishmaniasis, Chagas disease, and many others are examples of diseases transmitted by insects.Both the diet and the infection with pathogens trigger changes in many metabolic pathways, including lipid metabolism, compared to other insects. Blood contains mostly proteins and is very poor in lipids and carbohydrates. Thus, hematophagous insects attempt to efficiently digest and absorb diet lipids and also rely on a large de novo lipid biosynthesis based on utilization of proteins and carbohydrates as carbon source. Blood meal triggers essential physiological processes as molting, excretion, and oogenesis; therefore, lipid metabolism and utilization of lipid storage should be finely synchronized and regulated regarding that, in order to provide the necessary energy source for these events. Also, pathogens have evolved mechanisms to hijack essential lipids from the insect host by interfering in the biosynthesis, catabolism, and transport of lipids, which pose challenges to reproduction, survival, fitness, and other insect traits.In this chapter, we have tried to collect and highlight the current knowledge and recent discoveries on the metabolism of lipids in insect vectors of diseases related to the hematophagous diet and pathogen infection.

Adenosine A2A receptor as a potential regulator of Mycobacterium leprae survival mechanisms: new insights into leprosy neural damage.

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae preferentially infects skin macrophages and Schwann cells-glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host-pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signaling molecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor A2AR involved in neuroimmune response, lipid metabolism, and neuron-glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during M. leprae-Schwann cell interaction. Methods: M. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae in the presence or absence of specific agonists or antagonists of AdoS. Enzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR analysis were performed. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzyme-linked immunosorbent assay. Results: We demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular M. leprae viability; 4) increased levels of p-CREB. Conclusion: These findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.