Activation of CTHRC1 by HOXB9 Promotes Angiogenesis through Fatty Acid Metabolism in Lung Adenocarcinoma

Abstract Background: CTHRC1 is highly expressed in various cancers. Objectives: The aim of the study was to study the role of CTHRC1 played in lung adenocarcinoma (LUAD) development and its underlying biological functions. Methods: Enriched pathways and upstream transcription factors of CTHRC1 were explored by bioinformatics analysis. Dual-luciferase assay and Chromatin immunoprecipitation assay were used to verify the binding relationship between CTHRC1 and HOXB9. CCK-8 was utilized to detect cell viability. Expression levels of CTHRC1, HOXB9, and angiogenesis-related genes were assessed by quantitative real time-polymerase chain reaction. Angiogenesis assay was used to detect angiogenesis ability. Quantitative analysis of metabolites were used to detect the accumulation of neutral lipids, the levels of free fatty acids (FAs), and glycerol. Western blot was conducted to measure expression of metabolic enzymes of FA. Results: CTHRC1 was enriched in FA metabolic pathway, which was positively correlated and bound with HOXB9. CTHRC1 and HOXB9 expression was remarkably up-regulated in LUAD cells. Overexpression of CTHRC1 promoted FA metabolic pathway and angiogenesis, and FA inhibitor Orlistat restored it to NC group level. Meanwhile, CTHRC1 affected LUAD angiogenesis by activating HOXB9 to regulate FA metabolism. Conclusions: This study found that activation of CTHRC1 by HOXB9 induces angiogenesis by mediating FA metabolism. CTHRC1 may be a potential target for LUAD diagnosis.

Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells / 中华血液学杂志

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

Pathogenesis of Metabolic Remodeling of Energy Substrate Based on Theory of Deficient Qi Stagnation and Progress of Chinese Medicine Intervention / 中国实验方剂学杂志

In the case of cardiac dysfunction， energy metabolism changes and the metabolism of myocardial substrates is reconstructed， as manifested by variation in the selection and utilization of energy substrates such as fatty acids and glucose. Persistent metabolic disorders of substrates will decrease energy supply， thus resulting in the occurrence and development of heart failure. Metabolic remodeling of substrate is resulted from the decline of visceral function and the accumulation of pathological products. Deficient Qi stagnation is the core pathogenesis. Deficient Qi （heart Qi deficiency， insufficient energy） is the root cause， which exists in the whole disease course. Stagnation （phlegm， blood stasis， fluid， lipid toxic products， lactic acid， etc.） is the symptom， which evidences the aggravation of the disease. Deficient Qi and stagnation are intertwined and causal， which form a spiral vicious circle. The typical syndrome is excess resulted from deficiency and deficiency-excess in complexity. The treatment principle is reinforcing healthy Qi and tonifying deficiency， dredging and removing pathogen. At the early stage， the method of reinforcing healthy Qi and tonifying deficiency （benefiting Qi） should be used， and the method of dredging and removing pathogen （activating blood） can be applied according to the conditions of patients. At the middle and late stages， both reinforcing healthy Qi and tonifying deficiency （benefiting Qi and warming Yang） and dredging and removing pathogen （activating blood， resolving stasis， and excreting water） should be emphasized. Chinese medicine can be applied according to the pathogenesis， thereby promoting the utilization of fatty acids， glucose， and other substrates and reducing the accumulation of toxic products derived from metabolic remodeling of substrate. Thus， both the root cause and symptoms can be alleviated， further improving cardiac energy metabolism and heart function.

Research progress on ferroptosis regulated by glycolysis-fatty acid metabolism in metabolic diseases / 药学学报

In metabolic diseases, the accumulation of reactive oxygen species and oxidative stress are closely associated with ferroptosis. As a key regulatory factor, the imbalance between glycolysis and fatty acid metabolism can participate in ferroptosis directly or indirectly, thereby regulating the occurrence and development of various metabolic diseases. The essence of ferroptosis is a new regulatory cell death mode, which is caused by the excessive accumulation of iron-dependent lipid peroxide. It is closely related to glycolysis and fatty acid metabolism, which plays an important role in metabolic diseases. This regulatory cell death mode is significantly distinguished from other programmed cell death modes and has unique changes in cell morphology, symbolic characteristics and mechanisms. This paper first illustrates the main mechanism of glycolysis and fatty acid metabolism imbalance in the occurrence of ferroptosis, then reviews the research progress of ferroptosis in tumor, diabetes, rheumatoid arthritis and other metabolic diseases, and finally reveals the internal connection between glycolysis-fatty acid metabolism imbalance and ferroptosis, as well as its impacts on metabolic diseases, which provide new strategies for the prevention and treatment of metabolic diseases.

Advances in studies on ACSL1’s promoting hepatic lipid accumulation and inflammation and participating in disease development / 西安交通大学学报(医学版)

The acyl-CoA synthetase long-chain (ACSL) belongs to an enzyme encoded by a polygenic family. ACSL, located in the endoplasmic reticulum and outer mitochondrial membrane, can catalyze fatty acids to form acyl-CoA, participating in many physiological processes, such as fatty acid metabolism and membrane modification. The ACSL family plays different roles in the fatty acid metabolism of different cells, and its dysfunction can lead to conditions such as fatty liver, arteriosclerosis, and diabetes. As a major subtype of the ACSL family in the liver, ACSL family member 1 (ACSL1) is mainly involved in the maintenance of cholesterol stability, fatty acid activation, and bile acid metabolism. It is also associated with the development of certain liver diseases such as hepatocellular carcinoma and steatosis. This paper reviews differences in physiological functions and functional characteristics of ACSL family members. It also discusses the advances in studies on the role of ACSL1 in influencing lipid metabolism, regulating cellular iron death, and the development of related diseases such as liver fibrosis, hepatocellular carcinoma, cachexia, steatosis, thyroid cancer, and breast cancer.

Role of fatty acid metabolism in kidney disease and therapeutic intervention by traditional Chinese medicine / 中国药科大学学报

@#Fatty acid metabolism, including fatty acid oxidation (FAO) and fatty acid synthesis, plays critical roles in signal transduction, energy production and inflammation regulation.Acute kidney injury (AKI), chronic kidney disease (CKD) and renal cell carcinoma (RCC) are typical renal diseases with complex pathogenesis, susceptibility to multiple complications, and still no effective measure for clinical intervention.Current studies reveal that fatty acid metabolism is closely related to the occurrence and development of a variety of kidney diseases.This article reviews the metabolic characteristics of fatty acid in the kidney, the relationship between fatty acid metabolism disorder and renal diseases (i.e., AKI, CKD and RCC), and summarizes traditional Chinese medicines and related active ingredients targeting fatty acid metabolic pathway to alleviate renal diseases, aiming to provide theoretical reference for the in-depth study of mechanisms related to fatty acid metabolism in renal diseases as well as the development of effective interventions.

PGC1α plays a pivotal role in renal fibrosis via regulation of fatty acid metabolism in renal tissue / 中南大学学报(医学版)

Renal fibrosis is a common and irreversible pathological feature of end-stage renal disease caused by multiple etiologies. The role of inflammation in renal fibrosis tissue has been generally accepted. The latest view is that fatty acid metabolism disorder contributes to renal fibrosis. peroxisome proliferator activated receptor-gamma coactivator 1α (PGC1α) plays a key role in fatty acid metabolism, regulating fatty acid uptake and oxidized protein synthesis, preventing the accumulation of lipid in the cytoplasm, and maintaining a dynamic balanced state of intracellular lipid. In multiple animal models of renal fibrosis caused by acute or chronic kidney disease, or even age-related kidney disease, almost all of the kidney specimens show the down-regulation of PGC1α. Upregulation of PGC1α can reduce the degree of renal fibrosis in animal models, and PGC1α knockout animals exhibit severe renal fibrosis. Studies have demonstrated that AMP-activated protein kinase (AMPK), MAPK, Notch, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), epidermal growth factor receptor (EGFR), non-coding RNA (ncRNAs), liver kinase B1 (LKB1), hairy and enhancer of split 1 (Hes1), and other pathways regulate the expression of PGC1α and affect fatty acid metabolism. But some of these pathways interact with each other, and the effect of the integrated pathway on renal fibrosis is not clear.

Myocardial Substrate Metabolic Remodeling in Heart Failure / 中国实验方剂学杂志

Myocardial substrate metabolism is severely impaired after heart failure, and the selection and utilization of substrates, such as glucose and fatty acids, are remodeled, resulting in insufficient myocardial productivity, cardiac dysfunction and progressive left ventricular remodeling. It is believed traditionally that the heart changes from fatty acid metabolism to glucose metabolism during heart failure, which however is contradictory with some findings in recent years. No consistent conclusion can be drawn from studies on the changes of myocardial energy substrate metabolism and its regulatory mechanism after heart failure. Metabolic treatment for heart failure has developed slowly. Therefore, it is necessary to explore the reasons for heterogeneity of these conclusions for defining the metabolic patterns of heart failure substrates and developing metabolically targeted drugs. This review summarizes the metabolic patterns and regulatory mechanisms of normal myocardium under physiological conditions, focuses on the elaboration and comparison of myocardial substrates metabolic abnormalities in heart failure induced by ischemic heart disease, pressure load, volume load and dilated cardiomyopathy in such aspects as etiology, severity, duration of heart failure, species studied, animal models and metabolic detection methods, and makes a preliminary analysis on the consistency and differences of relevant conclusions in various studies, and discusses the future trend of metabolic treatment, with the aim to summarize the rules and molecular mechanism of glucose metabolism and fatty acid metabolism after heart failure and provide clues for the research of metabolic targeted therapy.

Analytical methods for evaluation of the fatty acid metabolism in rat liver / Métodos analíticos para avaliação do metabolismo em ratos hepáticos

The liver is an essential organ for body energy homeostasis, controlling the biosynthesis, uptake and the disposal of carbohydrates and lipids. The hepatic steatosis is a common condition frequently associated with metabolic diseases and is characterized by the excessive accumulation of triglycerides in the liver. In recent years, many efforts have been devoted to prevent and treat the hepatic steatosis, but it remains being pointed out as the major cause for chronic hepatic diseases in Western countries. A considerable part of the knowledge about the physiopathology of hepatic steatosis, the effects of diets and drugs on the metabolic capacity of the liver to metabolize fatty acids, as well as the potential therapeutic approaches for hepatic steatosis derived from experimental animal models using rodents. Here, in this article, we present the details of some of the most common techniques used to evaluate fatty acid metabolism in liver of rats, including quantification of total lipid content, measurement of fatty acid oxidation in isolated subcellular fractions and procedures to measure the activities of important lipogenic enzymes. Classical protocols previously described to be performed using samples from other tissues were adapted to liver samples and different techniques with equivalent aims were compared. The principles and the advantages in terms of reliability and costs were discussed and the procedures here described can be applied for a low-cost broad evaluation of the fatty acid metabolism in liver of rats submitted to different experimental conditions.

O fígado é um órgão essencial para a homeostase energética, controlando a biossíntese, a captação e a eliminação de carboidratos e lipídios. A esteatose hepática é uma condição frequentemente associada a doenças metabólicas e é caracterizada pelo acúmulo excessivo de triacilgliceróis no fígado. Nos últimos anos, muitos esforços têm sido dedicados para prevenir e tratar a esteatose hepática, mas essa condição continua sendo apontada como a principal causa de doenças hepáticas crônicas em países ocidentais. Uma parte considerável do conhecimento sobre a fisiopatologia da esteatose hepática, sobre os efeitos de dietas e drogas na capacidade metabólica do fígado em metabolizar ácidos graxos, bem como sobre as possíveis abordagens terapêuticas para a esteatose hepática, derivam de estudos com modelos animais experimentais usando roedores. Neste artigo, apresentamos os detalhes de algumas das técnicas que podem ser usadas para avaliar o metabolismo de ácidos graxos no fígado de ratos, incluindo a quantificação do conteúdo lipídico total, medida da oxidação de ácidos graxos em frações subcelulares isoladas e procedimentos para medir as atividades de importantes enzimas lipogênicas. Protocolos clássicos previamente descritos para serem realizados utilizando amostras de outros tecidos foram adaptados para amostras de fígado e diferentes técnicas com objetivos equivalentes foram comparadas. Os princípios e as vantagens em termos de confiabilidade e custos foram discutidos e os procedimentos aqui descritos podem ser aplicados para uma avaliação ampla e de baixo custo do metabolismo de ácidos graxos no fígado de ratos submetidos a diferentes condições experimentais.

Influence of n-3 fish oil fatty emulsion on fatty acid profile and inflammatory mediator in patients underwent total gastrectomy / 中国现代普通外科进展

Objective:To investigate the effects of n-3 fish oil fatty emulsion on fatty acid profile and lipid mediator,immune regulation mechanism and anti-inflammatory effect of inpatients underwent total gastrectomy.Methods:In a prospective,double-blind,and randomized controlled trial,60 patients underwent total gastrectomy were divided into two groups,therapy group and control group.The control group was given routine therapy while the therapy group was given routine therapy and fish oil.The day before the operation,1,4 and 8 days after the operation,The lipid metabolic Indices,including free fatty acids spectrum were detected;The inflammation indicator,including c-reactive protein(CRP) and interleukin(IL-1,lL-6),tumor necrosis factor alpha(TNF-α) were tested;The cellular immune function,including HLA-DR expression rate,the level of T cell subgroup were detected with flow cytometry.The clinical outcome indicators including APACHE Ⅱ score,postoperative infection and MODS incidence,postoperative hospitalization days,hospitalization mortality were observed.Results:There was no significant difference between Fish oil group and control group in age,sex and BMI,the serum levels of inflammatory cytokines,the HLA-DR expression rate,level of T cell subgroup,APACHE Ⅱ score,etc.(P＞0.05),so the two groups are comparable.Compared with control group,the n-6/n-3 PUFAs ratio drops,AA content decreased,but the content of EPA and DHA is increased,in fish oil group,decreased in fish oil group (P＜0.05);Compared with control group,serum concentration of CRP,IL-6 and TNF-α in patients of therapy group were significantly reduced,and clinical outcome improved.There was no difference in the expression of T cell subgroup between two groups.Conclusion:Application of n-3 fish oil fat emulsion,can lower the n-6/n-3 PUFAs ratio,reduce the AA content in serum,but the content of EPA and DHA is increased;N-3 fish oil fat emulsion can reduce serum after total gastrectomy,IL-1,IL-6,TNF-α inflammatory factor and the concentration of CRP,effectively reduce the inflammatory response in patients with;N-3 fish oil fat emulsion can improve the HLA-DR expression rate,reduce the immunosuppression,but had no significant effect on T cell subgroup level;N-3 fish oil fat emulsion to reduce the incidence of postoperative infection and MODS,improve patients with acute physiology,but had no significant effect on total days in hospital,mortality.

Mimicking Ketonuria in the Ketogenesis Defect 3-Hydroxy-3-MethylglutarylCoenzyme A Lyase Deficiency: An Artefact in the Analysis of Urinary Organic Acids

Abstract 3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HMGCL, HMGCL) deficiency is a rare inborn error of ketogenesis. Even if the ketogenic enzyme is fully disrupted, an elevated signal for the ketone body acetoacetic acid is a frequent observation in the analysis of urinary organic acids, at least if derivatization is performed by methylation. We provide an explanation for this phenomenon and trace it back to degradation of the derivatized 3-hydroxy-3-methylglutaric acid and high temperature of the injector of the gas chromatograph.

Metabolic reprogramming of the de novo fatty acid synthesis pathway in cancer devel-opment and progression / 中国肿瘤临床

Cancer cell metabolic reprogramming is a highly significant feature in tumor development and progression.This process is an extension of aerobic glycolysis(i.e.,Warburg effect).The metabolic pattern,such as that of glycolysis,oxidative phosphorylation, amino acid metabolism,fatty acid metabolism,and nucleic acid metabolism,is altered significantly during cell carcinogenesis.Fatty ac-id metabolism is required for energy storage,membrane proliferation,and signaling molecule generation.Thus,studying the mecha-nism of de novo fatty acid synthesis and its relationship with the development and progression of tumor,as well as the use and target-ing of the key enzyme in this metabolic pathway,is vital for the diagnosis,prevention,and treatment of cancer.Herein,we provide a brief review of metabolic reprogramming in cancer cells.We focus on the pathways of de novo fatty acid synthesis during the develop-ment and progression of tumor.

Metabolic reprogramming of the de novo fatty acid synthesis pathway in cancer devel-opment and progression / 中国肿瘤临床

Cancer cell metabolic reprogramming is a highly significant feature in tumor development and progression.This process is an extension of aerobic glycolysis(i.e.,Warburg effect).The metabolic pattern,such as that of glycolysis,oxidative phosphorylation, amino acid metabolism,fatty acid metabolism,and nucleic acid metabolism,is altered significantly during cell carcinogenesis.Fatty ac-id metabolism is required for energy storage,membrane proliferation,and signaling molecule generation.Thus,studying the mecha-nism of de novo fatty acid synthesis and its relationship with the development and progression of tumor,as well as the use and target-ing of the key enzyme in this metabolic pathway,is vital for the diagnosis,prevention,and treatment of cancer.Herein,we provide a brief review of metabolic reprogramming in cancer cells.We focus on the pathways of de novo fatty acid synthesis during the develop-ment and progression of tumor.

Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats

Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in β-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, β-cell hypersecretion, a higher percentage of islets and β-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

BOIOGITO INCREASES FATTY ACID - METABOLISM IN PROXIMAL TUBULAR CELLS THROUGH THE PEROXISOME PROLIFERATORS-ACTIVATED RECEPTOR (PPAR) Α AGONISTIC ACTIVITY / Монголын эм зүй, эм судлал

The promotion of fatty acid metabolism, to which PPARα contributes, has been suggested that it would be participate to maintain the proximal tubular cell function in kidney. The loading on the proximal tubular cell of fatty acids could arise the inflammation and cell death in obesity. One of the “Kampo” medicines, Boiogito (BO) is used for the remedy of overweight women exhibiting chronic fatigues as well as edema in the lower extremities or knees. BO would exhibit the prevention of the proximal tubular cell damage and improvement of kidney function by reducing the portion of fatty acids. In this study, BO was orally administered high fatty acid combined with bovine serum albumin for mice to evaluate the mRNA expression of PPARα quantified by PCR. The increase of PPARα mRNA expression was observed BO administration, followed by reduce the volume of fatty acids in kidney.KEY WORDS: Boiogito, Fatty acid metabolism, PPARα, Proximal Tubular CellINTRODUCTIONObesity is a risk factor for incidence of albuminuria and chronic kidney disease 1, 2, and an accumulating visceral fat would be involved in the regulation of primary stage of nephropathy 3, microalbuminuria. Fatty acids are major contributor to these kidney disorders caused by obesity 4. The binding fatty acids with albumin represents in blood generally, taking up by proximal tubular cells after glomerular filtration from albumin. A peroxisome proliferator - activated receptor (PPARα) has been suggested that it would regulate the fatty acid metabolism. Because the glomerular filtration rate and renal blood flow would increase in overweight patients 5, a large quantity of free fatty acids should be loaded into proximal tubular cells. Therefore, the investigation concerning to PPARα stimulator can be regarded as the fatty acid metabolism - regulation. One of the “Kampo” medicines, Boiogito (BO) is used for the remedy of the inflammation and cell death in obesity, is composed of eight crude drugs: Aluminum Silicate Hydrate with Silicon Dioxide, Astragalus Root, Atractylodes Rhizome, Ginger, Glycyrrhiza, Jujube, Sinomenium Stem and Rhizome. In this study, to clarify the therapeutic mechanisms of BO, we focused on the up - regulating for fatty acid metabolism through the PPARα activation.METHODSKampo formulaeBO was prepared according to the prescription for a one-day dose 6: 3.0 g Aluminum Silicate Hydrate with Silicon Dioxide, 5.0 g Astragalus Root, 3.0 g Atractylodes Rhizome, 1.0 g Ginger, 2.0 g Glycyrrhiza, 4.0 g Jujube, 4.0 g Sinomeniumstem and Rhizome.

Análisis estructural y funcional de proteínas solubles que unen lípidos de intestino e hígado / Structure-function analysis of soluble lipid binding proteins from intestine and liver / Análise estrutural e funcional de proteínas solúveis que ligam lipídeos de intestino e fígado

Luego de la ingesta, el epitelio del intestino delgado está encargado de asimilar grandes cantidades de nutrientes, como aminoácidos, glúcidos y ácidos grasos. Las proteínas solubles que unen lípidos cumplirían un rol determinante en este proceso, sobre todo protegiendo la integridad del tejido contra el efecto simil-detergente de los ácidos grasos provenientes de la dieta. En enterocitos se expresan dos proteínas que unen ácidos grasos de cadena larga, IFABP y LFABP, para las cuales no se conocen bien aún sus funciones específicas, o el porqué de la necesidad de dos proteínas aparentemente equivalentes. Este laboratorio se ha enfocado en el estudio comparativo de estas dos proteínas empleando distintas variantes estructurales y métodos bioquímicos, biofísicos, y de biología molecular y celular. Así, se han podido definir los determinantes moleculares de cada proteína responsables de la interacción con membranas, los mecanismos de transferencia de ligandos y los factores que modulan estas propiedades. Más recientemente, se han extendido estos ensayos a cultivos celulares donde se ha correlacionado la expresión de estas proteínas con la secreción de citoquinas, la proliferación y la diferenciación celular. El estudio de estas proteínas es de gran importancia por su potencial como blancos terapéuticos y su utilidad en el diagnóstico de injurias tisulares.

After ingestion, the epithelium of the small intestine is responsible for assimilating large amounts of nutrients such as amino acids, sugars and fatty acids. Soluble lipid binding proteins fulfill a determining role in this process, especially protecting the tissue integrity against the detergent-like effect of fatty acids from the diet. Two proteins that bind long-chain fatty acids are expressed in enterocytes, IFABP and LFABP, whose specific functions are still poorly understood, or the reason for the need of two apparently equivalent proteins. Our laboratory has focused on the comparative study of these two proteins using structural variants and biochemical, biophysical, and molecular and cellular biology approaches. Thus, the molecular determinants responsible for the interaction with membranes were defined for each protein, their ligand transfer mechanism and the factors that modulate these properties. More recently, these assays have been extended to cell culture studies which correlate the expression of these proteins with cytokine secretion, cell proliferation and differentiation. The study of these proteins is of great importance due to their potential as therapeutic targets and their usefulness in the diagnosis of tissue injury.

Após a ingestão, o epitélio do intestino delgado é responsável pela assimilação de uma grande quantidade de nutrientes, tais como aminoácidos, glicídios e ácidos graxos. As proteínas solúveis que ligam lipídeos desempenhariam um papel determinante neste processo, principalmente protegendo a integridade do tecido contra o efeito detergente dos ácidos graxos da dieta. Nos enterócitos se expressam duas proteínas que ligam ácidos graxos de cadeia longa, IFABP e LFABP; cujas funções específicas ainda não são muito conhecidas, ou não se conhece o motivo pelo qual são necessárias duas proteínas aparentemente equivalentes. Nosso laboratório tem se focado no estudo comparativo destas duas proteínas utilizando variantes estruturais e métodos bioquímicos, biofísicos, e de biologia molecular e celular. Assim, foi possível definir os determinantes moleculares de cada proteína responsáveis pela interação com membranas, os mecanismos da transferência de ligantes e os fatores que modulam essas propriedades. Mais recentemente, estendemos estes ensaios para culturas celulares, correlacionando a expressão destas proteínas com a secreção de citocinas, a proliferação e a diferenciação celular. O estudo destas proteínas é de grande importância por seu potencial como alvos terapêuticos e sua utilidade no diagnóstico de lesões teciduais.

Relationship between diabetic cardiomyopathy and peroxisome proliferators-activated receptors / 中国药理学通报

Diabetic cardiomyopathy ( DC) is an independent complication of diabetes mellitus accompanied with cardiac metabolic imbalances ( increase of fatty acids and reduction of glucose) ,which would impair cardiac function and structure seriously. Peroxisome proliferator-activated receptors ( PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily,and they could transcriptionally regulate energy metabolism and function. PPARs also play an important role in regulating metabolism in DC heart,and directly or indirectly affect cardiac function and structure.