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Background: Lipid accumulation product (LAP), visceral adiposity index (VAI) and Chinese visceral adiposity index (CVAI) are proposed indices of visceral adipose accumulation. This study aimed to explore their relationship and temporal changes with hyperuricemia (HUA) development in a Chinese population. Methods: A total of 4268 participants aged ≥45 years from the baseline survey of the China Health and Retirement Longitudinal Study were followed up for 4 years (from 2011 to 2015). The relationships among VAI, LAP, CVAI and HUA were analyzed using logistic regression. The predictive abilities of the VAI, LAP and CVAI for HUA were compared using receiver operating characteristic curves. Nonlinear relationships between the indices and HUA were analyzed using restricted cubic spline regression. Results: During the four-year follow-up, 415 (9.72 %) patients experienced incident HUA . Elevated baseline VAI (odds ratio (OR): 1.19 (95 % confidence interval (95 %CI: 1.10, 1.29)), LAP (OR: 1.21 (95 % CI: 1.09, 1.34)) and CVAI (OR: 1.19 (95 % CI: 1.02, 1.40)) were significantly correlated with increased HUA risk (all P < 0.05). Compared to individuals with consistently low VAI,CVAIor LAP levels, those with elevated or consistently high levels of these indicators are more likely to have HUA. The area under curve (AUC) was slightly greater and more significant for the CVAI (AUC=0.641) than for the VAI (AUC=0.604) and LAP (AUC=0.628) (P < 0.05). Conclusion: VAI, LAP and CVAI can predict HUA, with CVAI more efficient than VAI and LAP. Early management can lessen the burden of HUA in Chinese people aged 45 years or older with elevated CVAI levels.
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Atherosclerosis remains a major challenge to global healthcare despite decades of research and constant trials of novel therapeutic approaches. One feature that makes atherosclerosis treatment so elusive is an insufficient understanding of its origins and the early stages of the pathological process, which limits our means of effective prevention of the disease. Macrovascular pericytes are cells with distinct shapes that are located in the arterial wall of larger vessels and are in many aspects similar to microvascular pericytes that maintain the functionality of small vessels and capillaries. This cell type combines the residual contractile function of smooth muscle cells with a distinct stellar shape that allows these cells to make numerous contacts between themselves and the adjacent endothelial layer. Moreover, pericytes can take part in the immune defense and are able to take up lipids in the course of atherosclerotic lesion development. In growing atherosclerotic plaques, the morphology and function of pericytes change dramatically due to phagocytic and synthetic phenotypes that are actively involved in lipid accumulation and extracellular matrix synthesis. In this review, we summarize our knowledge of this less-studied cell type and its role in atherosclerosis.
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OBJECTIVES: This study aims to establish cut-off points for lipid accumulation product and tri-ponderal mass index to identify insulin resistance (IR) in Brazilian postpubertal adolescents. METHODS: We conducted an analysis of postpubertal adolescents enrolled in the national school-based cross-sectional study of cardiovascular risks in adolescents (ERICA-BRAZIL) from February 2013 to November 2014. IR was defined by homeostatic model assessment index for IR values ≥2.32 for girls and ≥2.87 for boys. The analysis involved calculating the area under receiver operating characteristic curves, sensitivity values, specificity, positive and negative predictive values, and positive and negative likelihood ratios to determine reference values of indices with optimal performance. RESULTS: The sample was comprised of 14 026 adolescents, with 25.3% (95% confidence intervals: 24.6%-26.1%) exhibiting IR, more prevalent among girls and overweight individuals. The ideal lipid accumulation product cut-off points associated with IR were 13.5 for the total population, 13.8 for male adolescents, and 13.5 for girls. Regarding tri-ponderal mass index, the optimal cut-off values for identifying IR were 14.1, 13.9, and 14.5 kg/m³ in the general sample, boys, and girls, respectively. CONCLUSIONS: This study establishes cut-off points for adiposity indices, demonstrating their effectiveness in screening for IR in postpubertal Brazilian adolescents.
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Betaine is the major water-soluble component of Lycium chinensis. Although there are reports of a protective effect of betaine on fatty liver disease, the underlying mechanisms are unclear. We attempted to elucidate the molecular regulation of betaine on hyperglycemia-induced hepatic lipid accumulation via Forkhead box O (FoxO)6 activation. HepG2 cells and liver tissue isolated from db/db mice treated with betaine were used. The present study investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO6/peroxisome proliferator-activated receptor gamma (PPARγ) signaling in liver cells. Interestingly, betaine notably decreased lipid accumulation in tissues with FoxO6-induced mRNA expression of lipogenesis-related genes. Furthermore, betaine inhibited the FoxO6 interaction with PPARγ and cellular triglycerides in high-glucose- or FoxO6-overexpression-treated liver cells. In addition, we confirmed that betaine administration via oral gavage significantly ameliorated hepatic steatosis in db/db mice. We conclude that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the interaction between FoxO6 and PPARγ, thereby suppressing lipogenic gene transcription.
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Scenedesmus sp. is a species of the Scenedesmus genus within the phylum Chlorophyta, commonly found as a planktonic algal species in freshwater and known for its rapid growth rate. This study employs room-temperature, atmospheric-pressure plasma mutagenesis for the breeding of Scenedesmus sp., utilizing transcriptomic analysis to investigate the biosynthesis mechanism of triglycerides. Further analysis of differentially expressed genes in transcriptome by measuring the macroscopic biological indicators of mutant and original algal strains. The findings of the study suggest that the mutant strain's photosynthesis has been enhanced, leading to improved light energy utilization and CO2 fixation, thereby providing more carbon storage and energy for biomass and lipid production. The intensification of glycolysis and the TCA (tricarboxylic acid) cycle results in a greater shift in carbon flux towards lipid accumulation. An elevated expression level of related enzymes in starch and protein degradation pathways may enhance acetyl CoA accumulation, facilitating a larger substrate supply for fatty acid production and thereby increasing lipid yield.
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Scenedesmus , Scenedesmus/metabolismo , Scenedesmus/genética , Gases em Plasma/farmacología , Fotosíntesis , Triglicéridos/metabolismo , Mutación , Metabolismo de los Lípidos/genética , Transcriptoma , Perfilación de la Expresión Génica , Mutagénesis , Biomasa , Ácidos Grasos/metabolismoRESUMEN
The objective of this research was to explore the potential association between lipid accumulation product (LAP) and chronic kidney disease (CKD) among adult population of United States (US). Using cross-sectional data from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES), we explored the association of LAP with CKD, low estimated glomerular filtration rate (eGFR), and albuminuria. This analysis encompassed multivariate logistic regression analyses, smoothed curve fitting, subgroup analyses, and interaction tests. We found a significant positive association between higher ln-transformed LAP (LAP was transformed using a natural logarithm) and the prevalence of CKD, low-eGFR and albuminuria. Notably, this association of ln-transformed LAP with CKD and albuminuria was significantly influenced by diabetes status and sex (P for interaction < 0.05), while no significant interaction was observed regarding the association with low-eGFR (P for interaction > 0.05). Additionally, in model 3 (adjusted for all included covariates except eGFR and urinary albumin-creatinine ratio (UACR)), a nonlinear relationship was identified between ln-transformed LAP and the presence of both CKD and albuminuria, with inflection points of 4.57 and 4.49, respectively. This indicates that this correlation is more pronounced on the right of the inflection point. In conclusion, the findings indicate a significant association between LAP and the prevalence of CKD in US adults.
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Tasa de Filtración Glomerular , Producto de la Acumulación de Lípidos , Encuestas Nutricionales , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/metabolismo , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Adulto , Estudios Transversales , Albuminuria/epidemiología , Prevalencia , Anciano , Factores de RiesgoRESUMEN
The objective of this study is to investigate the association between diabetic kidney disease (DKD) and various adiposity indexes, including the visceral adiposity index (VAI), lipid accumulation product index (LAPI), visceral fat area (VFA), and subcutaneous fat area (SFA) in type 2 diabetes mellitus (T2DM) patients. 1176 T2DM patients was stratified into normoalbuminuria (NO), microalbuminuria (MI), and macroalbuminuria (MA) groups based on their urinary albumin-creatinine ratio (UACR) levels. To analyse the correlation between DKD and VAI, LAPI, VFA, and SFA. Multiple linear, restricted cubic spline (RCS), subgroup analyses, and multinomial logistic regression were employed. After adjusting for confounding variables, UACR levels were positively associated with VAI, LAPI, and VFA. RCS curves demonstrated a J-shaped dose-response relationship between VAI and LAPI levels with UACR levels, while a linear correlation was observed between UACR levels and VFA. Using the NO and MI as reference groups, the MA group was analysed as the observational group. DKD severity was positively associated with VAI, LAPI and VFA. When evaluating DKD prognostic risk, with the low-risk and medium-risk groups serving as reference categories, a significant positive correlation was identified with prognostic risk and VAI, LAPI, and VFA in the high-risk or very high-risk groups. In patients with T2DM, DKD severity and prognostic risk were positively correlated with VAI, LAPI, and VFA levels.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Grasa Intraabdominal , Obesidad , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Nefropatías Diabéticas/orina , Persona de Mediana Edad , Estudios Transversales , Grasa Intraabdominal/metabolismo , Obesidad/complicaciones , Anciano , Albuminuria , Adiposidad , Factores de RiesgoRESUMEN
The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs. The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation. Fourteen pigs, including seven lean and seven obese pigs with body weights of approximately 80 kg, were fed the same diet at an amount approximately equivalent to 3% of their respective body weights daily for 42 d. In vitro, 3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium. Then, bile acids were added to mature adipocytes for 4 d. The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs (P < 0.05). According to the results of gut microbial function prediction, the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig. Sixty-five bile acids were further screened by metabolomics, of which 4 were upregulated (P < 0.05) and 2 were downregulated (P < 0.05) in obese pigs compared to lean pigs. The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-ß-D-glucuronide (CDCA-3Gln) and ω-muricholic acid (ω-MCA) had a negative correlation with abdominal fat weight and abdominal fat rate, while isoallolithocholic acid (IALCA) was positively associated with crude fat in the liver and abdominal fat rate. There was a positive correlation between loin muscle area and CDCA-3Gln and ω-MCA (P < 0.05), however, IALCA and 3-oxodeoxycholic acid (3-oxo-DCA) were negatively associated with loin eye muscle area (P < 0.05). Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma (PPARG) and the number of lipid droplets (P < 0.05), promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro. In conclusion, the concentration of bile acids, especially gut microbiota related-secondary bile acids, in obese pigs was different from that in lean pigs, which may contribute to lipid accumulation within obese pigs.
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Lipid accumulation product (LAP) has a positive effect on spinal bone mineral density (BMD). However, once LAP levels exceed 27.26, the rate of spinal BMD increase slow down or even decline. This indicates a biphasic relationship between lipid metabolism and BMD, suggesting potential benefits within a certain range and possible adverse effects beyond that range. This study aimed to investigate the potential association between LAP index and BMD in US adults, as well as to explore the presence of a potential saturation effect in this relationship. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. A multiple stepwise regression model was employed to examine the association between LAP index and total spinal BMD. Additionally, a generalized additive model and a smooth curve fitting algorithm were utilized to examine the relationship, and saturation effect study was conducted to determine the saturation level. The calculation formula of LAP used in the study was: (LAP = (waist circumstances (WC) (cm) - 58) × triglyceride (TG) (mmol/L)) for women, and (LAP = (WC (cm) - 65) × TG (mmol/L)) for men. The study involved a total of 7913 participants aged 20 years or older. Through multiple stepwise regression analysis, it was found that individuals with higher LAP scores exhibited higher total spinal BMD. In both the crude and partially adjusted models, total spinal BMD was significantly higher in the highest LAP quartile (Q4) compared to the lowest LAP quartile (Q1) (P < 0.05). Utilizing a generalized additive model and smooth curve, a nonlinear relationship between LAP and total spinal BMD was observed. Furthermore, the study identified the saturation value of LAP to be 27.26, indicating a saturation effect. This research highlights a nonlinear relationship between LAP and total spinal BMD, along with the presence of a saturation effect.
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AIMS: The aim of the research was to look into the connection between the occurrence of gallstones in adult US citizens and lipid accumulation products (LAP). METHODS: We conducted a cross-sectional study of 3,582 U.S. adults with relevant indicators collected from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) database. Multifactorial logistic regression was used to investigate the linear relationship between LAP and gallstone incidence, while smoothed curve fitting was used to describe the nonlinear relationship, and subgroup and interaction analyses were used to evaluate the potential differences between groups. RESULTS: Among the 3582 participants aged ≥ 20 years included, there was a positive association between LAP and gallstones. Following adjustments for all covariates, the likelihood of getting gallstones rose by 29% for each unit rise in log2-LAP (OR = 1.29, 95% CI: 1.13â1.49). Compared to those in the lowest tertile, those in the highest LAP tertile had a significantly higher risk of developing gallstones (OR = 1.97, 95% CI: 1.31â2.95). Subgroup analyses indicated that the association between LAP and gallstones was not affected by the stratification of the variables examined. CONCLUSION: Gallstones and LAP exhibited a positive association in our investigation, indicating that LAP may be utilized as a clinical indicator to determine the occurrence of gallstones.
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Cálculos Biliares , Producto de la Acumulación de Lípidos , Encuestas Nutricionales , Humanos , Cálculos Biliares/epidemiología , Estudios Transversales , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Factores de Riesgo , Incidencia , Adulto Joven , Anciano , Modelos LogísticosRESUMEN
Nonalcoholic fatty liver disease (NAFLD), the most common chronic hepatic disease, has become a leading health problem worldwide. The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferatoractivated receptor agonists, cenicriviroc and farnesoid X receptor agonists. Biologically active substances, such as peptides, alkaloids, polyphenolic compounds, silymarin, antibiotics, fatty acids, vitamins, probiotics, synbiotics and lamiaceae have also demonstrated actions that combat NAFLD. Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Cirugía Bariátrica/métodos , Dieta Mediterránea , Animales , Ejercicio Físico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Probióticos/uso terapéuticoRESUMEN
BACKGROUND: The Lipid Accumulation Product (LAP) is a measure that indicates excessive fat accumulation in the body. LAP has been the focus of research in epidemiological studies aimed at forecasting chronic and metabolic diseases. This study aimed to evaluate the association between LAP and type 2 diabetes mellitus (T2DM) among adults in western Iran. METHODS: The study involved 9,065 adults who participated in the initial phase of the Ravansar non-communicable diseases study (RaNCD) cohort. To investigate the association between LAP and T2DM, multiple logistic regressions were employed. Additionally, the receiver operating characteristic (ROC) curve was used to evaluate LAP's predictive ability concerning T2DM. RESULTS: The participants had an average age of 47.24 ± 8.27 years, comprising 49.30% men and 50.70% women. The mean LAP was 53.10 ± 36.60 for the healthy group and 75.51 ± 51.34 for the diabetic group (P < 0.001). The multiple regression analysis revealed that the odds of T2DM in the second quartile of LAP were 1.69 (95% CI: 1.25, 2.29) times greater than in the first quartile. Furthermore, the odds in the third and fourth quartiles were 2.67 (95% CI: 2.01, 3.55) and 3.73 (95% CI: 2.83, 4.92) times higher, respectively. The ROC analysis for predicting T2DM showed that the LAP index had an area under the curve (AUC) of 0.66 (95% CI: 0.64, 0.68). CONCLUSION: A strong association was identified between elevated LAP levels and T2DM in the adult population of western Iran. LAP is recommended as a potential tool for screening diabetes susceptibility.
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Diabetes Mellitus Tipo 2 , Producto de la Acumulación de Lípidos , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Irán/epidemiología , Adulto , Factores de Riesgo , Pronóstico , Curva ROC , Biomarcadores/análisis , Estudios de Seguimiento , Estudios de Cohortes , Estudios TransversalesRESUMEN
Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents as benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, and minimal immunogenicity, positioning them as a therapeutic innovation for liver diseases. Therefore, this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics, and support the development of MSC-based therapy in the treatment of NAFLD.
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The coffee industry produces a considerable quantity of coffee pulp (CP), a by-product with high levels of caffeine, phenolic compounds, and dietary fiber, which are reportedly involved in the lipid homeostasis regulation required to maintain human health. This work's objective was to evaluate the hypolipidemic activity of coffee pulp flour (CPF) and aqueous extract (CPE) after static simulated digestion by the assessment of their in vitro capacity to decrease emulsification and digestion of fats, and lipid-lowering capacity in HepG2 cells after the induction of intracellular fat accumulation. The CPF and CPE digested fractions displayed in vitro hypolipidemic properties by preserving the reduction of micellar cholesterol solubility (27-34%) and the secondary bile acid-binding capacity (22-30%), increasing their primary bile acid-binding ability (2.7-fold and 2.4-fold, respectively), and inhibiting the lipase and the HMGCR (77-79% and 36-85%, respectively) activities. Moreover, the hypolipidemic properties of non-digested fractions enhanced the CPF potential to decrease lipid absorption. Both ingredients (CPF and CPE) demonstrated lipid-lowering effects since they effectively counteract the accumulation of intracellular triglycerides and cholesterol triggered by palmitic acid in hepatic cells after the simulated digestion. This study suggests that phenolic compounds, caffeine, and dietary fiber may be responsible for the lipid-lowering properties exhibited by the CP ingredients and their composition differences affect the above-mentioned properties exhibited in the simulated digestion. These results contribute to demonstrating that the CPF and the CPE may act as modulators of pathways involved in hepatic lipid accumulation and could be a key element in its prevention.
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Exposed to ubiquitously perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with non-alcoholic fatty liver disease (NAFLD), yet the underlying molecular mechanism remains elusive. The extrapolation of empirical studies correlating per- and polyfluoroalkyl substance (PFAS) exposure with NAFLD occurrence to real-life exposure was hindered by the limited availability of mechanistic data at environmentally relevant concentrations. Herein, a novel pathway mediating hepatocyte lipid accumulation by PFOA and PFOS at human-relevant dose (<10 µM) was identified by integrating CRISPR-Cas9 genome screening, concentration-dependent transcriptional assay in HepG2 cell and epidemiological data mining. 1) At genetic level, nudt7 showed the highest enriched potency among 569 NAFLD-related genes, and the transcription of nudt7 was significantly downregulated by PFOA and PFOS exposure (<7 µM). 2) At molecular pathway, upon exposure to ≤10-4 µM PFOA and PFOS, the downregulation of nudt7 transcriptional expression triggered the reduction of Ace-CoA hydrolase activity. 3) At cellular level, increased lipids were measured in HepG2 cells with PFOA and PFOS (<2 µM). Overall, we identified a novel mechanism mediated by transcriptional downregulation of nudt7 gene in hepatocellular lipid increase treated with PFOA and PFOS, which could potentially explain the NAFLD occurrence associated with exposure to PFASs in humans.
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Glioblastoma-derived exosomes (GDEs), containing nucleic acids, proteins, fatty acids and other substances, perform multiple important functions in glioblastoma microenvironment. Tumor-derived exosomes serve as carriers of fatty acids and induce a shift in metabolism towards oxidative phosphorylation, thus driving immune dysfunction of dendritic cells (DCs). Lipid peroxidation is an important characteristic of ferroptosis. Nevertheless, it remains unclear whether GDEs can induce lipid accumulation and lipid oxidation to trigger ferroptosis in DCs. In our study, we investigate the impact of GDEs on lipid accumulation and oxidation in DCs by inhibiting GDEs secretion through knocking down the expression of Rab27a using a rat orthotopic glioblastoma model. The results show that inhibiting the secretion of GDEs can reduce lipid accumulation in infiltrating DCs in the brain and decrease mature dendritic cells (mDCs) lipid peroxidation levels, thereby suppressing glioblastoma growth. Mechanistically, we employed in vitro treatments of bone marrow-derived dendritic cells (BMDCs) with GDEs. The results indicate that GDEs decrease the viability of mDCs compared to immature dendritic cells (imDCs) and trigger ferroptosis in mDCs via the NRF2/GPX4 pathway. Overall, these findings provide new insights into the development of immune-suppressive glioblastoma microenvironment through the interaction of GDEs with DCs.
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Neoplasias Encefálicas , Células Dendríticas , Exosomas , Ferroptosis , Glioblastoma , Metabolismo de los Lípidos , Factor 2 Relacionado con NF-E2 , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Ferroptosis/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Exosomas/metabolismo , Glioblastoma/inmunología , Glioblastoma/metabolismo , Glioblastoma/patología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Ratas , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Transducción de Señal , Humanos , Microambiente Tumoral/inmunología , Línea Celular Tumoral , Masculino , Peroxidación de LípidoRESUMEN
In bivalve, development of female gonad is accompanied with accumulating lipids which provided energy resource for non-feeding larvae development. As the major transcriptional regulators of lipid metabolism, Srebps play pivotal role in lipid homeostasis during oogenesis. However, little work was conducted on Srebps function in bivalves. The noble scallop Chlamys nobilis accumulated large amount of lipids in its gonad during oogenesis. Here, we identified a single Srebp gene (named Srebp-1) with a high similarity to human Srebp-1c. Disrupting Srebp-1 with Betulin (inhibiting the maturation of Srebp protein) repressed expression of lipogenic genes and de novo lipogenesis, and resulted in reduction of gonad index and lipid deposition, suggesting a crucial role of Srebp-1 for gonad development and lipid synthesis in female gonad. Additionally, scallops with Srebp-1 disruption released fewer eggs with a reduction in their lipid content and D-larvae formation, revealing an impair of fecundity caused by Srebp-1 disruption. Cold exposure stimulated lipid accumulation which required Srebp-1 to regulate de novo lipogenesis and lipid uptake, providing a crosstalk of Srebp-1 activity and environmental variation on lipid accumulation in noble scallop. Thus, our study identified Srebp-1 as a central regulator coordinating the lipid synthesis and accumulation with gonad development in noble scallop.
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Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma (n = 18) and IDH1 mutant (IDH1-mt) astrocytoma (n = 12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical membraneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vasculature have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Lipid excess in gliomas stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune responses, non-lipophilic drugs, and free radicals.
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Neoplasias Encefálicas , Glioma , Metabolismo de los Lípidos , Microambiente Tumoral , Humanos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Glioma/patología , Glioma/metabolismo , Isocitrato Deshidrogenasa/genética , Femenino , Masculino , Persona de Mediana EdadRESUMEN
Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.
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Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Proteómica , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Animales , Ratones , Metabolismo de los Lípidos/fisiología , Femenino , Lipidómica , Transcriptoma , MultiómicaRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Osteocalcin plays an important role in energy metabolism. In this study, we investigated the mechanism of action of chemically synthesized osteocalcin (csOCN) in ameliorating NAFLD. We demonstrated for the first time that csOCN attenuates lipid accumulation in the liver and hepatocytes by modulating CD36 protein expression. In addition, we found that the expression of p-AMPK, FOXO1 and BCL6 decreased and the expression of CD36 increased after OA/PA induction compared to the control group, and these effects were reversed by the addition of csOCN. In contrast, the therapeutic effect of csOCN was inhibited by the addition of AMPK inhibitors and BCL6 inhibitors. This finding suggested that csOCN regulates CD36 expression via the AMPK-FOXO1/BCL6 axis. In NAFLD mice, oral administration of csOCN also activated the AMPK pathway and reduced CD36 expression. Molecular docking revealed that osteocalcin has a docking site with CD36. Compared to oleic acid and palmitic acid, osteocalcin bound more strongly to CD36. Laser confocal microscopy results showed that osteocalcin colocalized with CD36 at the cell membrane. In conclusion, we demonstrated the regulatory role of csOCN in fatty acid uptake pathways for the first time; it regulates CD36 expression via the AMPK-FOXO1/BCL6 axis to reduce fatty acid uptake, and it affects fatty acid transport by may directly binding to CD36. There are indications that csOCN has potential as a CD36-targeted drug for the treatment of NAFLD.