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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".

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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.

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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.

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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.

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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.

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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.

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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.

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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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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.

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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.

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