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1.
J Agric Food Chem ; 67(38): 10667-10677, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483636

RESUMO

This study investigated the modulatory effects of Decaisnea insignis seed oil (DISO), which was rich in palmitoleic acid (55.25%), palmitic acid (12.25%), and oleic acid (28.74%), on alcohol-induced metabolism disorder in mice. Fifty mice were orally administered with 38% alcohol (0.4 mL/day) and without or with DISO (3, 6, and 12 g/kg) for consecutive 12 weeks. DISO inhibited the alcohol-induced weight loss and liver function abnormality (p < 0.01) and shifted the profiles of cecal microbiome: elevating the abundance of Lactobacillus, Ruminoccoceae_UCG_004 (p < 0.05) and decreasing abundance of Parabacteroides (p < 0.05). This treatment also regulated metabolome response of amino acid and lipid metabolism in cecal content: upregulating 5-hydroxyindole-3-acetic acid (p < 0.05), 6-hydroxynicotinic acid, 5-methoxytryptamine, nicotinamide, and nicotinic acid (p < 0.1) and downregulating androsterone, tryptophan, and indole-3-acetamide (p < 0.05). DISO protected against alcoholic liver injury and gut microbiota dysbiosis by enriching the relative abundance of Lactobacillus, which was positively associated with the improvement of intestinal permeability and tryptophan metabolism.


Assuntos
Álcoois/efeitos adversos , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Magnoliopsida/química , Óleos Vegetais/administração & dosagem , Consumo de Bebidas Alcoólicas/efeitos adversos , Aminoácidos/metabolismo , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Ceco/efeitos dos fármacos , Ceco/microbiologia , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/microbiologia , Masculino , Metaboloma/efeitos dos fármacos , Camundongos , Microbiota/efeitos dos fármacos , Sementes/química
2.
J Agric Food Chem ; 67(38): 10614-10623, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483658

RESUMO

Type 2 diabetes (T2D) is a pandemic disease chiefly characterized by hyperglycemia. In this study, the combination of serum lipidomic and metabolomic approach was employed to investigate the effect of arabinoxylan on type 2 diabetic rats and identify the critical biomarkers of T2D. Metabolomics analysis revealed that branched-chain amino acids, 12α-hydroxylated bile acids, ketone bodies, and several short- and long-chain acylcarnitines were significantly increased in T2D, whereas lysophosphatidylcholines (LPCs) were significantly decreased. Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitine, free fatty acids (FFA), diacylglycerols, triacylglycerols, and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines (less than 22 carbons). These variations indicated the disturbed amino acid and lipid metabolism in T2D, and the accumulation of incompletely oxidized lipid species might eventually contribute to impaired insulin action and glucose homeostasis. Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids, carnitines, and FFAs and increased the levels of LPCs. The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.


Assuntos
Anticolesterolemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Xilanos/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Carnitina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Metabolômica , Ratos
3.
Khirurgiia (Mosk) ; (9): 66-72, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532169

RESUMO

The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. Material and methods. The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. Results. In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.


Assuntos
Transtornos da Coagulação Sanguínea/prevenção & controle , Doenças do Sistema Digestório/complicações , Infecções Intra-Abdominais/complicações , Substâncias Protetoras/administração & dosagem , Succinatos/administração & dosagem , Doença Aguda , Animais , Apendicite/complicações , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Colecistite Aguda/complicações , Doenças do Sistema Digestório/fisiopatologia , Cães , Doenças Hematológicas/etiologia , Doenças Hematológicas/fisiopatologia , Doenças Hematológicas/prevenção & controle , Hemostasia/fisiologia , Humanos , Obstrução Intestinal/complicações , Infecções Intra-Abdominais/fisiopatologia , Metabolismo dos Lipídeos/fisiologia , Pancreatite/complicações , Úlcera Péptica Perfurada/complicações , Peritonite/complicações , Síndrome
4.
J Environ Sci (China) ; 85: 138-146, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471020

RESUMO

Arsenic (As) is an omnipresent metalloid toxicant, which has elicited serious environmental pollution and health risky problems. Previous studies have uncovered that the As exposure could also cause markedly reduction of serum triglycerides in mice. However, the regulation mechanisms are still largely unknown. The present study is aimed to elucidate the molecular mechanisms of lncRNAs in As-induced lipid metabolic disequilibrium. We demonstrated that lncRNA PU.1 AS was significantly induced in the liver of As-feed mice companied with lower serum triglycerides contents; further in vitro experiment confirmed that PU.1 AS regulated liver cells lipid accumulation by nile red fluorescence staining. Intensive mechanistic investigations illustrated that PU.1 AS could interact with EZH2 protein to regulate its downstream target gene expression, and As-induced PU.1 AS attenuated EZH2-supppressed Sirt6 expression, thereafter leading to a decreased SREBP-1c protein expression, as well as the diminished synthesis of triglycerides in hepatocytes. In conclusion, this study provided a new lncRNA-related regulatory signaling pathway participating in As-induced abnormal lipid metabolism.


Assuntos
Arsênico/metabolismo , Metabolismo dos Lipídeos/genética , Animais , Camundongos , RNA Longo não Codificante/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1 , Triglicerídeos
5.
Adv Exp Med Biol ; 1161: 3-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562617

RESUMO

Keratitis is a sight-threatening inflammatory condition of the cornea that can be caused by both infectious and non-infectious agents. Physical or chemical trauma are typically related to non-infectious keratitis, which may then become secondarily infected or remain non-infected. Etiology of infectious keratitis is most often associated with bacteria; but viruses, fungi, and parasites are common causative pathogens as well. As a global concern, common risk factors include: systemic immunosuppression (secondary to malnutrition, alcoholism, diabetes, steroid use), previous corneal surgery (refractive corneal surgery, penetrating keratoplasty), extended wear contact lens use, pre-existing ocular surface diseases (dry eye, epithelial defect) and ocular trauma (agriculture- or farm-related) [1-8]. Annual rates of incidence include nearly one million clinical visits due to keratitis in the United States, while it has been reported that roughly two million people develop corneal ulcers in India. Clinically, patients may show signs of eye pain (ranging from mild to severe), blurred vision, photophobia, chemosis and redness. Pathogenesis is generally characterized by rapid progression, focal white infiltrates with underlying stromal inflammation, corneal thinning, stromal edema, mucopurulent discharge and hypopyon, which can lead to corneal scarring, endophthalmitis, and perforation. In fact, corneal opacity is not only a complication of keratitis, but among the leading causes of legal blindness worldwide. Despite that empirical treatment effectively controls most of the pathogens implicated in infectious keratitis, improved clinical outcomes are not guaranteed. Further, if treatment is not initiated in a timely manner, good visual outcome is reduced to approximately 50% of keratitis patients [9]. Moreover, resultant structural alterations, loss of tissue and an unresolved host response remain unaddressed through current clinical management of this condition.


Assuntos
Infecções Oculares , Ceratite , Metabolismo dos Lipídeos/fisiologia , Úlcera da Córnea/epidemiologia , Úlcera da Córnea/etiologia , Úlcera da Córnea/fisiopatologia , Infecções Oculares/complicações , Infecções Oculares/microbiologia , Infecções Oculares/parasitologia , Infecções Oculares/virologia , Humanos , Ceratite/epidemiologia , Ceratite/etiologia , Ceratite/microbiologia , Ceratite/fisiopatologia , Lipídeos/química , Estudos Retrospectivos
6.
Adv Exp Med Biol ; 1161: 133-148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562628

RESUMO

Bioactive lipids, or lipid mediators, are utilized for intercellular communications. They are rapidly produced in response to various stimuli and exported to extracellular spaces followed by binding to cell surface G protein-coupled receptors (GPCRs) or nuclear receptors. Many drugs targeting lipid signaling such as non-steroidal anti-inflammatory drugs (NSAIDs), prostaglandins, and antagonists for lipid GPCRs are in use. For example, the sphingolipid analog, fingolimod (also known as FTY720), was the first oral disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (MS), whose mechanisms of action (MOA) includes sequestration of pathogenic lymphocytes into secondary lymphoid organs, as well as astrocytic modulation, via down-regulation of the sphingosine 1-phosphate (S1P) receptor, S1P1, by in vivo-phosphorylated fingolimod. Though the cause of MS is still under debate, MS is considered to be an autoimmune demyelinating and neurodegenerative disease. This review summarizes the involvement of bioactive lipids (prostaglandins, leukotrienes, platelet-activating factors, lysophosphatidic acid, and S1P) in MS and the animal model, experimental autoimmune encephalomyelitis (EAE). Genetic ablation, along with pharmacological inhibition, of lipid metabolic enzymes and lipid GPCRs revealed that each bioactive lipid has a unique role in regulating immune and neural functions, including helper T cell (TH1 and TH17) differentiation and proliferation, immune cell migration, astrocyte responses, endothelium function, and microglial phagocytosis. A systematic understanding of bioactive lipids in MS and EAE dredges up information about understudied lipid signaling pathways, which should be clarified in the near future to better understand MS pathology and to develop novel DMTs.


Assuntos
Encefalomielite Autoimune Experimental , Metabolismo dos Lipídeos , Lipídeos , Esclerose Múltipla , Doenças Neurodegenerativas , Animais , Modelos Animais de Doenças , Lipídeos/química , Esclerose Múltipla/fisiopatologia , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/fisiopatologia
7.
Adv Exp Med Biol ; 1161: 233-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562633

RESUMO

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease involving motor neuron (MN) degeneration in the spinal cord, brain stem and primary motor cortex. The existence of inflammatory processes around MN and axonal degeneration in ALS has been shown. Unfortunately, none of the successful therapies in ALS animal models has improved clinical outcomes in patients with ALS. Therefore, the detection of blood biomarkers to be used as screening tools for disease onset and progression has been an expanding research area with few advances in the development of drugs for the treatment of ALS. In this review, we will address the available data analyzing regarding the relationship of lipid metabolism and lipid derived- products with ALS. We will address the advances on the studies about the role that lipids plays at the onset, progression and lifespan extension of ALS patients.


Assuntos
Esclerose Amiotrófica Lateral , Biomarcadores , Lipídeos , Esclerose Amiotrófica Lateral/sangue , Esclerose Amiotrófica Lateral/diagnóstico , Animais , Biomarcadores/sangue , Progressão da Doença , Humanos , Metabolismo dos Lipídeos , Lipídeos/sangue
8.
Adv Exp Med Biol ; 1161: 243-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562634

RESUMO

Flavonoids are plant secondary metabolites that act as protectants against harmful effects of UV-B radiation inasmuch as biotic stress, conferring at the same time pigmentation of fruits and leaves [67]. The term "flavonoid" refers to phenolics having a basic skeleton of diphenylpropane (C6-C3-C6), which consists of two aromatic rings linked through three carbons that usually form an oxygenated heterocycle [25, 52]. Flavonoids are broken down into several different sub-categories based on their chemical structure. The main subclasses commonly found in food items are: flavonols, flavones, flavanones, flavan-3-ols, proanthocyanidins, and anthocyanins [44, 67]. Figure 19.1 depicts the major classification of flavonoids according to their chemical structure. Their occurrence in food matrices has been extensively reviewed [39, 44], and has been subject of extensive research in the last decades. Table 19.1 contains a few examples of compounds from each of the subcategory, with the fruit (berry) in which they are commonly found. The monomeric unit of flavonoids can dimerize and polymerize to form other important high molecular weight molecules; this is the case of proanthocyanidins, that are polymers of flavan-3-ols or flavanols. Not only do these compounds act as plant protectants, but they can also be very beneficial to human health. Cohorts studies performed in the early '90 have shown that dietary consumption of flavonoids was inversely associated with morbidity and mortality from coronary heart disease [31, 32]. These findings have opened an intensive field of research on the effects of flavonoids and flavonoids-rich food extracts in cardiovascular diseases (CVD) progression, particularly in the modulating CVD-associated oxidative stress and inflammation. In this short review, we will summarize the current findings in flavonoids beneficial effects in preventing CVD through inhibition of initial stages of CVD progression. Given the magnitude of scientific literature in the field, we will focus on two strictly mechanistic aspects: inhibition of chemical-induced LDL oxidation, and the effect of flavonoids in the monocyte/macrophages activation pathways.


Assuntos
Colesterol , Flavonoides , Metabolismo dos Lipídeos , Colesterol/metabolismo , Dieta , Flavonoides/metabolismo , Humanos , Inflamação/fisiopatologia , Oxirredução
9.
Adv Exp Med Biol ; 1159: 1-3, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31502196

RESUMO

Sphingolipid biology has enjoyed a remarkable rise to fame over the last two decades. Various molecules from this lipid family have been implicated in a variety of cellular functions in health and disease. Ceramides, which constitute the hub of sphingolipid metabolism, are apoptogenic molecules that have many proposed mechanisms of actions. Enigmas revolving around this area of research are slowly being cleared with the advent of better laboratory techniques and data analyses. In this chapter, a general introduction of the topics presented in this book is undertaken highlighting the main ideas of each chapter.


Assuntos
Ceramidas/metabolismo , Metabolismo dos Lipídeos , Esfingolipídeos/metabolismo
10.
J Agric Food Chem ; 67(33): 9432-9440, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31368703

RESUMO

Potassium fertilization is commonly practiced in oil palm (Elaeis guineensis) plantations to increase yield. However, its effects on fruit oil content and composition are not well documented. Here, we conducted bunch, metabolomics, and oil composition analyses in two contrasting crosses (Deli × La Mé and Deli × Yangambi) grown under different K fertilization conditions. K availability impacted bunch oil content, resulting in lower water content and higher oil proportion in fruit mesocarp, in Deli × La Mé only, thus showing differential responses of crosses to K. Oil composition at maturity did not significantly change under low K conditions despite clear alterations in fruit metabolism associated with lipid production during maturation, demonstrating the resilience of oil biosynthetic metabolism. However, the analysis of variance in oil content (across K treatments and crosses) demonstrates that sugar availability, lipid synthesis rates, and metabolic recycling are all important in determining the oil content.


Assuntos
Arecaceae/metabolismo , Fertilizantes/análise , Frutas/química , Lipídeos/química , Óleo de Palmeira/química , Potássio/metabolismo , Arecaceae/química , Arecaceae/crescimento & desenvolvimento , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Metabolismo dos Lipídeos
11.
Bioresour Technol ; 291: 121894, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31387839

RESUMO

Microalgae accumulate starch and lipid as storage metabolites under nutrient depletion, which can be used as sustainable feedstock for biorefinery. Omics analysis coupled with enzymatic and genetic verifications uncovered a partial picture of pathways and important enzymes or regulators related to starch and lipid biosynthesis as well as the carbon partitioning between them under nutrient depletion conditions. Depletion of macronutrients (N, P, and S) resulted in considerable enhancement of starch and/or lipid content in microalgae, but the accompanying declined photosynthesis hampered the achievements of high concentrations. This review summarized the current knowledge on the pathways and the committed steps as well as their carbon allocation involved in starch and lipid biosynthesis, and focused on the manipulation of different nutrients and the alleviation of oxidative stress for enhanced storage metabolites production. The biological and engineering approaches to cope with the conflict between biomass production and storage metabolites accumulation are proposed.


Assuntos
Metabolismo dos Lipídeos , Microalgas/metabolismo , Nutrientes , Amido/metabolismo , Biomassa , Lipídeos
12.
J Chem Ecol ; 45(8): 673-683, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31407198

RESUMO

Animals modulate intraspecific signal shape and intensity, notably during reproductive periods. Signal variability typically follows a seasonal scheme, traceable through the expression of visual, acoustic, chemical and behavioral patterns. The chemical channel is particularly important in lizards, as demonstrated by well-developed epidermal glands in the cloacal region that secrete lipids and proteins recognized by conspecifics. In males, the seasonal pattern of gland activity is underpinned by variation of circulating androgens. Changes in the composition of lipid secretions convey information about the signaler's quality (e.g., size, immunity). Presumably, individual identity is associated with a protein signature present in the femoral secretions, but this has been poorly investigated. For the first time, we assessed the seasonal variability of the protein signal in relation to plasma testosterone level (T), glandular activity and the concentration of provitamin D3 in the lipid fraction. We sampled 174 male common wall lizards (Podarcis muralis) over the entire activity season. An elevation of T was observed one to two months before the secretion peak of lipids during the mating season; such expected delay between hormonal fluctuation and maximal physiological response fits well with the assumption that provitamin D3 indicates individual quality. One-dimensional electrophoretic analysis of proteins showed that gel bands were preserved over the season with an invariant region; a result in agreement with the hypothesis that proteins are stable identity signals. However, the relative intensity of bands varied markedly, synchronously with that of lipid secretion pattern. These variations of protein secretion suggest additional roles of proteins, an issue that requires further studies.


Assuntos
Glândulas Exócrinas/metabolismo , Lipídeos/análise , Lagartos/fisiologia , Proteínas de Répteis/análise , Animais , Desidrocolesteróis/análise , Eletroforese em Gel de Campo Pulsado , Cromatografia Gasosa-Espectrometria de Massas , Metabolismo dos Lipídeos , Lipídeos/química , Masculino , Análise de Componente Principal , Estações do Ano , Comportamento Sexual Animal , Testosterona/sangue
13.
Eur J Histochem ; 63(3)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31455073

RESUMO

RNA interference is a powerful approach to understand gene function both for therapeutic and experimental purposes. Since the lack of knowledge in the gene silencing of various hepatic cell lines, this work was aimed to compare two transfection agents, the liposome-based Lipofectamine™ RNAiMAX and the HepG2-specific, polymer-based GenMute™, in two cellular models of human hepatoma, HepG2 and Huh7.5. In the first part, we assessed transfection efficiency of a fluorescent Cy3-labeled negative control siRNA by cell imaging analysis; we found that cells treated with GenMute present a higher uptake of the fluorescent negative control siRNA when compared to Lipofectamine RNAiMAX-transfected cells, both in HepG2 and in Huh7.5 cells. In the second part, we evaluated GAPDH silencing with the two transfection reagents by RT-PCR similar GAPDH mRNA expression after each transfection treatment. Finally, we measured cell viability by the MTT assay, observing that cells transfected with GenMute have higher viability with respect to Lipofectamine RNAiMAX-administered cells. These results suggest that GenMute reagent might be considered the most suitable transfection agent for hepatic gene silencing.


Assuntos
Técnicas de Transferência de Genes , Lipídeos/química , Polímeros/química , RNA Interferente Pequeno/genética , Transfecção/métodos , Sequência de Bases , Carbocianinas/química , Carbocianinas/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Inativação Gênica , Gliceraldeído-3-Fosfato Desidrogenases/genética , Humanos , Metabolismo dos Lipídeos , Lipídeos/toxicidade , Lipossomos/química , Lipossomos/metabolismo , Lipossomos/toxicidade , Neoplasias Hepáticas/genética , Polímeros/metabolismo , Polímeros/toxicidade , Interferência de RNA
14.
Adv Exp Med Biol ; 1158: 143-182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452140

RESUMO

Mitochondrial dysfunction is discussed as a key player in the pathogenesis of type 2 diabetes mellitus (T2Dm), a highly prevalent disease rapidly developing as one of the greatest global health challenges of this century. Data however about the involvement of mitochondria, central hubs in bioenergetic processes, in the disease development are still controversial. Lipid and protein homeostasis are under intense discussion to be crucial for proper mitochondrial function. Consequently proteomics and lipidomics analyses might help to understand how molecular changes in mitochondria translate to alterations in energy transduction as observed in the healthy and metabolic diseases such as T2Dm and other related disorders. Mitochondrial lipids integrated in a tool covering proteomic and functional analyses were up to now rarely investigated, although mitochondrial lipids might provide a possible lynchpin in the understanding of type 2 diabetes development and thereby prevention. In this chapter state-of-the-art analytical strategies, pre-analytical aspects, potential pitfalls as well as current proteomics and lipidomics-based knowledge about the pathophysiological role of mitochondria in the pathogenesis of type 2 diabetes will be discussed.


Assuntos
Biologia Computacional , Diabetes Mellitus Tipo 2 , Fígado , Mitocôndrias , Músculo Esquelético , Proteômica , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Metabolismo dos Lipídeos , Fígado/fisiopatologia , Mitocôndrias/metabolismo , Músculo Esquelético/fisiopatologia
15.
Zhen Ci Yan Jiu ; 44(7): 492-6, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368279

RESUMO

OBJECTIVE: To observe the impact of electroacupuncture (EA) on liver lipid metabolism and expression of hepatic sirtuin 1(Sirt1) and peroxisome proliferator activated receptor γ(PPARγ) of abdominal obese rats induced by high-fat diet. METHODS: Eighteen male SD rats were divided into blank control, model and EA groups (n=6 per group). The abdominal obesity model was established by feeding the rats with high-fat diet for 12 weeks. EA (2 Hz/15 Hz, 1.5 mA) was applied to bilateral "Daimai"(GB26) for 20 min every time, once every other day for 8 weeks. Rats of the model group were also restrained for 20 min. The body mass and abdominal circumference were measured every week, and the contents of serum cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), aspartate aminotransferase (AST) were detected by using an automated biochemical analyzer. Histopathological changes of the liver tissues were observed under microscope after oil red "O" staining. The expression of hepatic Sirt1 and PPARγ mRNAs and proteins were detected using quantitative real time PCR and Western blot, separately. RESULTS: After modeling, the body weight and abdominal circumference, and serum TC, TG, ALT and AST contents, and expression of hepatic PPARγ mRNA and protein were significantly increased (P<0.001, P<0.01, P<0.05), and the expression levels of hepatic Sirt1 mRNA and protein obviously down-regulated (P<0.05, P<0.01) in the model group. Following EA intervention, the increased body weight and abdominal circumference, and serum TC, TG, ALT and AST contents, and hepatic PPARγ mRNA and protein expression were remarkably suppressed (P<0.05, P<0.01), and the decreased hepatic Sirt1 mRNA and protein were remarkably up-regulated (P<0.001,P<0.05). The lipid droplets in hepatocytes were reduced in the EA group relevant to the model group. CONCLUSION: EA intervention can significantly improve the liver lipid metabolism of abdominal obese rats, which is possibly related with its effect in up-regulating the expression of hepatic Sirt1 mRNA and protein, and in down-regulating the expression of hepatic PPARγ mRNA and protein.


Assuntos
Eletroacupuntura , Pontos de Acupuntura , Animais , Metabolismo dos Lipídeos , Masculino , Obesidade , PPAR gama , Ratos , Ratos Sprague-Dawley , Sirtuína 1
16.
Biol Res ; 52(1): 44, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426858

RESUMO

BACKGROUND: Free fatty acid receptor 1 (FFAR1) is G-protein coupled receptor predominantly expressed in pancreatic ß-cells that is activated by a variety of free fatty acids (FFAs). Once activated, it promotes glucose-stimulated insulin secretion (GSIS). However, increased levels of FFAs lead to lipotoxicity, inducing loss of ß-cell function. FFAR1 plays a key role in the development of type 2 diabetes (T2D), and previous studies have indicated the importance of developing anti-diabetic therapies against FFAR1, although its role in the regulation of ß-cell function remains unclear. The present study investigated the role of FFAR1 under lipotoxic conditions using palmitic acid (PA). The rat insulinoma 1 clone 832/13 (INS-1 832/13) cell line was used as a model as it physiologically resembles native pancreatic ß-cells. Key players of the insulin signaling pathway, such as mTOR, Akt, IRS-1, and the insulin receptor (INSR1ß), were selected as candidates to be analyzed under lipotoxic conditions. RESULTS: We revealed that PA-induced lipotoxicity affected GSIS in INS-1 cells and negatively modulated the activity of both IRS-1 and Akt. Reduced phosphorylation of both IRS-1 S636/639 and Akt S473 was observed, in addition to decreased expression of both INSR1ß and FFAR1. Moreover, transient knockdown of FFAR1 led to a reduction in IRS-1 mRNA expression and an increase in INSR1ß mRNA. Finally, PA affected localization of FFAR1 from the cytoplasm to the perinucleus. CONCLUSIONS: In conclusion, our study suggests a novel regulatory involvement of FFAR1 in crosstalk with mTOR-Akt and IRS-1 signaling in ß-cells under lipotoxic conditions.


Assuntos
Células Secretoras de Insulina/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácido Palmítico/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose , Linhagem Celular , Células Secretoras de Insulina/metabolismo , Ratos , Transdução de Sinais
17.
Adv Exp Med Biol ; 1155: 71-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468387

RESUMO

This study has evaluated the effects of a supplementation with taurine (TAU) on the actions of fish oil (FO) against the hypoglycemia, hypoproteinemia, and hepatic accumulation of lipids and liver damage caused by D-galactosamine (GAL) in the rat. To this end, male Sprague-Dawley rats (200-225 g), in groups of 6, were orally treated with physiological saline (2.5 mL, control group), FO (60 mg/kg), TAU (2.4 mmol/kg) or FO-TAU for three consecutive days and before a single oral dose of GAL (400 mg/kg) given on day 3. In parallel, rats receiving only GAL on day 3 or N-acetylcysteine (NAC, 2.4 mmol/kg) for 3 days before GAL served as controls. On day 4 blood samples were collected by cardiac puncture and used to either measure glucose (GLC) or to obtain plasma fractions. Immediately thereafter, the livers were excised, made into a homogenate in phosphate buffered saline pH 7.4, and centrifuged to obtain clear supernatant. Plasma samples were assayed for their total protein (TP), triglycerides (TG), cholesterol (CHOL), phospholipids (PLP), free fatty acids (FFA) and total bilirubin (TB) and direct bilirubin (DB) contents, and for the activities of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP). The liver homogenates were used to measure TG, CHOL, PLP and total lipids (TL) contents. Without exceptions, GAL was found to markedly affect (p < 0.001) all of the experimental parameters examined, with increases occurring in all instances except for the values of the plasma GLC, TP and PLP which were decreased. A pretreatment with either FO or TAU led to significant attenuation of the effects of GAL and which, in most cases, were of similar magnitude. On the other hand, a combined pretreatment with FO plus TAU usually resulted in a greater protection than with either agent alone (p ≤ 0.05). NAC, serving as a reference treatment, was, in most instances, equipotent with FO alone and. in addition, was the only agent that significantly attenuated the increases in both liver weight and liver weight to body weight ratio caused by GAL.


Assuntos
Óleos de Peixe/farmacologia , Galactosamina/efeitos adversos , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Taurina/farmacologia , Animais , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
18.
Adv Exp Med Biol ; 1155: 133-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468392

RESUMO

Metabolic syndrome is a lifestyle-related disease caused by high nutrient condition and lack of exercise. The insulin resistance due to obesity has attracted attention as an underlying mechanism of metabolic syndrome. Insulin resistance refers to reduced insulin sensitivity in insulin target tissues. In this case, in order to maintain normal blood glucose levels, a compensatory large amount of insulin is released, leading to the occurrence of hyperinsulinemia. Taurine is widely distributed in animal tissues. Although it is not involved in protein synthesis, taurine plays an important role in maintaining the body's physiological function. In this experiment, insulin resistance model was induced by high fat and high sugar diet. Two percent taurine was added in drinking water to explore the mechanism of taurine in insulin resistance and to provide theoretical basis for using taurine to improve insulin resistance. The result showed that high-fat and high-sugar diet could decrease insulin sensitivity, and taurine could improve it by oral glucose tolerance test. Moreover, serum TG, TC were higher, while HDL-C in rats fed with high sugar and high fat diet was lower than normal rats, the changes of which can be significantly relieved by 2% taurine administration. mRNA and protein expressions of IRS1, and GLUT4 which were significantly changed by high sugar and high fat diet can also be regulated by 2% taurine. The results indicated that taurine can improve insulin sensitivity through remediating lipid metabolism disorder and regulating the expressions of IRS and GLUT4.


Assuntos
Resistência à Insulina , Metabolismo dos Lipídeos , Músculo Esquelético/efeitos dos fármacos , Taurina/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Açúcares da Dieta/efeitos adversos , Músculo Esquelético/fisiologia , Ratos
19.
Adv Exp Med Biol ; 1155: 119-131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468391

RESUMO

Excessive consumption causes alcoholic liver disease (ALD), which injures hepatocytes and induces imbalance of lipid metabolism. Taurine is known to protect the liver from various liver injuries, and relieve lipid profile. Our previous studies also found that taurine can prevent or cure ALD, reduce fat deposition, but the mechanism remains unclear. In the present study, ALD rat model was established by administration of alcohol, pyrazole and high fat diet. Two percent taurine was administered at the same time or after ALD model establishment. Serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum and hepatic TC, TG, HDL-C and LDL-C were analyzed. Real-Time RT-PCR was conducted to detect the mRNA expressions of fatty acid synthetase (FAS), acetyl-CoA catboxylase (ACC), carnitine palmitoyl transferase 1 (CPT-1), 3-Hydroxy-3-methyl glutaric acid acyl Coenzyme A reductase (HMGCR), peroxisome proliferators activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP-1c). The results showed that serum ALT, AST, serum and hepatic TC, TG and LDL-C were higher, while HDL-C in ALD model rats was lower than normal rats, the changes of which can be significantly relieved by taurine administration. mRNA expressions of ACC, FAS, CPT-1, HMGCR, PPARα and SREBP-1c which were significantly changed by ethanol can also be regulated by taurine. The results indicated that taurine can prevent and repair hepatic injury of ALD rats and balance lipid metabolism indexes in the liver, the mechanisms may involves in the regulation of related enzymes and transcriptional regulators participated in lipid metabolism.


Assuntos
Metabolismo dos Lipídeos , Hepatopatias Alcoólicas/tratamento farmacológico , Taurina/farmacologia , Animais , Fígado/metabolismo , Fígado/fisiopatologia , Ratos
20.
Orthop Clin North Am ; 50(4): 529-537, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466668

RESUMO

Ankle osteoarthritis affects a significant portion of the global adult population. Unlike other joints, arthritis of the ankle often develops as a response to traumatic injury (intra-articular fracture) of the ankle joints. The full mechanism leading to posttraumatic osteoarthritis of the ankle (PTOAA) is poorly understood. These deficits in knowledge pose challenges in the management of the disease. Adequate surgical reduction of fractured ankle joints remains the gold standard in prevention. The purpose of this review is to thoroughly delineate the known pathogenesis of PTOAA, and provide critical updates on this pathology and new avenues to provide therapeutic management of the disease.


Assuntos
Fraturas do Tornozelo/complicações , Fraturas do Tornozelo/cirurgia , Osteoartrite/patologia , Fraturas do Tornozelo/metabolismo , Fenômenos Biomecânicos , Gerenciamento Clínico , Fixação Interna de Fraturas/instrumentação , Humanos , Metabolismo dos Lipídeos , Osteoartrite/metabolismo , Resultado do Tratamento
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