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1.
Adv Exp Med Biol ; 1232: 183-190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893409

RESUMO

Oxygen delivery to tissue mitochondria relies on simple diffusion in the target cells and tissues. As such, intracellular availability of O2 in tissue depends on its solubility and diffusivity in complex and heterogeneous macromolecular environments. The path of oxygen diffusion is key to its rate of transfer, especially where pathways of differing favorability are present. Most commonly, aqueous media, such as interstitial fluid and cytoplasm, are assumed to provide the dominant diffusion path. Here, the 'hydrophobic channeling' hypothesis is revisited, and several lines of evidence pointing toward lipid-accelerated oxygen diffusion pathways are discussed. The implications of hydrophobic channeling are considered in light of extended membrane networks in cells and tissues.


Assuntos
Células , Difusão , Metabolismo dos Lipídeos , Oxigênio , Células/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Mitocôndrias/metabolismo , Oxigênio/metabolismo
2.
Food Chem ; 305: 125435, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31494497

RESUMO

Soluble dietary fibre (SDF) of micronized and non-micronized powders of lotus root nodes were investigated based on its adsorption and activity inhibition of pancreatic lipase (PL) by using circular dichroism, fluorescence spectroscopy and modification. Results showed that SDF2 (SDF from micronized powders of lotus root nodes) had stronger PL adsorption and enzyme activity inhibition than SDF1 (SDF from non-micronized powders of lotus root nodes). Specifically, SDF2 showed more binding sites than SDF1 in PL. There were hydrogen bonds and van der Waals interactions between SDF and PL, with Trp on PL probably serving as the main binding site. Carboxyl groups exhibited a stronger inhibition on PL by carboxymethyl and hydroxypropyl modification. The common mechanisms between SDF1 and SDF2 can be attributed to the combination between Trp and carboxyl groups, while the differences may be generated by the variations in structures or chemical groups induced by micronization.


Assuntos
Fibras na Dieta , Lipase/metabolismo , Metabolismo dos Lipídeos , Lotus/química , Adsorção , Hidrólise , Preparações de Plantas/química , Raízes de Plantas/química , Pós/química , Solubilidade
3.
Chemosphere ; 239: 124759, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31518920

RESUMO

Ammonia is an important environmental stress factor in aquaculture. Long-term ammonia stress could affect the normal growth, and also increase the risk for the occurrence of various diseases. In order to learn the mechanism that ammonia caused the outbreak of the shrimp disease, transcriptomics and metabolomics approaches were used to analyze the differential expressions of the genes in hemocytes and different metabolites in the serum of the Pacific white shrimp Litopenaeus vannamei under ammonia exposure. Transcriptional analysis showed that 17 cell apoptosis related genes, seven phagocytosis related genes, 10 immunity related genes and seven cell cycle and lipid metabolism related genes showed differential expressions after ammonia exposure. Metabolomics analysis on the serum showed that 25 differential metabolites were identified in positive and negative ion patterns. They are involved in purine metabolism, amino acids metabolism and lipid metabolism. Injection of two up-regulated metabolites triethanolamine and oxypurinol to normal shrimp could induce apoptosis in normal shrimp. The total hemocytes counts in shrimp showed a significant decrease and the apoptotic cell ratio increased significantly under ammonia exposure. These results suggested that ammonia exposure increased the apoptosis of hemocytes, which affected the immunity of shrimp, and thus caused susceptibility to pathogenic infection. These data will help us understand the mechanism of ammonia stress leading to the immunity decline of shrimp.


Assuntos
Amônia/toxicidade , Hemócitos/efeitos dos fármacos , Penaeidae/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Aminoácidos/genética , Aminoácidos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Aquicultura , Perfilação da Expressão Gênica , Hemócitos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolômica , Penaeidae/fisiologia , Fagocitose/efeitos dos fármacos
4.
Biomed Khim ; 65(6): 441-456, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31876515

RESUMO

Osteoarthritis and type 2 diabetes mellitus represent two the most common chronic diseases. They possess many shared epidemiologic traits, have common risk factors, and embody heterogeneous multifactorial pathologies, which develop due to interaction of genetic an environmental factors. In addition, these diseases are often occurring in the same patient. In spite of the differences in clinical manifestation both diseases have similar disturbances of cellular metabolism, primarily associated with ATP production and utilization. The review discusses molecular mechanisms determining pathophysiological processes associated with glucose and lipid metabolism as well as the means aiming to alleviate the disturbances of energy metabolism as a new a therapeutic approach.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Metabolismo Energético , Glucose/metabolismo , Metabolismo dos Lipídeos , Osteoartrite/patologia , Dor , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Osteoartrite/metabolismo
5.
Cancer Immunol Immunother ; 68(12): 2005-2014, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701161

RESUMO

Checkpoint inhibitors (CPI) have significantly changed the therapeutic landscape of oncology. We adopted a non-invasive metabolomic approach to understand immunotherapy response and failure in 28 urological cancer patients. In total, 134 metabolites were quantified in patient sera before the first, second, and third CPI doses. Modeling the association between metabolites and CPI response and patient characteristics revealed that one predictive metabolite class  (n = 9/10) were very long-chain fatty acid-containing lipids (VLCFA-containing lipids). The best predictive performance was achieved through a multivariate model, including age and a centroid of VLCFA-containing lipids prior to first immunotherapy (sensitivity: 0.850, specificity: 0.825, ROC: 0.935). We hypothesize that the association of VLCFA-containing lipids with CPI response is based on enhanced peroxisome signaling in T cells, which results in a switch to fatty acid catabolism. Beyond use as a novel predictive non-invasive biomarker, we envision that nutritional supplementation with VLCFA-containing lipids might serve as an immuno sensitizer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/terapia , Ácidos Graxos/metabolismo , Imunoterapia/métodos , Linfócitos T/imunologia , Neoplasias Urológicas/terapia , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Receptores Coestimuladores e Inibidores de Linfócitos T/antagonistas & inibidores , Feminino , Humanos , Imunização , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Peroxissomos/metabolismo , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Transdução de Sinais , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/mortalidade
6.
Biol Bull ; 237(2): 90-110, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31714858

RESUMO

Calanus finmarchicus and Calanus glacialis are keystone zooplankton species in North Atlantic and Arctic marine ecosystems because they form a link in the trophic transfer of nutritious lipids from phytoplankton to predators on higher trophic levels. These calanoid copepods spend several months of the year in deep waters in a dormant state called diapause, after which they emerge in surface waters to feed and reproduce during the spring phytoplankton bloom. Disruption of diapause timing could have dramatic consequences for marine ecosystems. In the present study, Calanus C5 copepodites were collected in a Norwegian fjord during diapause and were subsequently experimentally exposed to the water-soluble fraction of a naphthenic North Sea crude oil during diapause termination. The copepods were sampled repeatedly while progressing toward adulthood and were analyzed for utilization of lipid stores and for differential expression of genes involved in lipid metabolism. Our results indicate that water-soluble fraction exposure led to a temporary pause in lipid catabolism, suggested by (i) slower utilization of lipid stores in water-soluble fraction-exposed C5 copepodites and (ii) more genes in the ß-oxidation pathway being downregulated in water-soluble fraction-exposed C5 copepodites than in the control C5 copepodites. Because lipid content and/or composition may be an important trigger for termination of diapause, our results imply that the timing of diapause termination and subsequent migration to the surface may be delayed if copepods are exposed to oil pollution during diapause or diapause termination. This delay could have detrimental effects on ecosystem dynamics.


Assuntos
Copépodes , Diapausa , Petróleo , Animais , Regiões Árticas , Ecossistema , Metabolismo dos Lipídeos
8.
Wei Sheng Yan Jiu ; 48(4): 601-605, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31601342

RESUMO

OBJECTIVE: To explore the effect and mechanism of wheat bran fiber on lipid metabolism in ApoE~(-/-)mice fed a high fat diet. METHODS: Twenty 7-week-old male ApoE~(-/-)mice were randomly divided into two groups and fed either a high fat diet as AS model group or a high fat diet adding 0. 8% wheat bran fiber as W-fiber group. And five C57 BL/6 mice with the same genetic background were used as control group. After 18 weeks feeding, HE staining were performed for atherosclerotic lesions from transverse section of the aorta and hepatic histological examination. Liver homogenate total cholesterol(TC), triglyceride(TG)and free fatty acids(FFAs)were analyzed. Western blot was used to determine the protein expressions involved in hepatic lipid metabolism, including sterol regulatory element binding protein 1(SREBP-1), fatty acid synthase(FAS), acetyl-coA carboxylase(ACC), sterol regulatory element binding protein 2(SREBP-2), low-density lipoproteins receptor(LDLR) and scavenger receptor B1(SR-B1). RESULTS: At the end of the experiment, compared with control group, atherosclerotic plaque of the aorta and hepatic steatosis was obvious in the mice of AS model group, and wheat bran fiber alleviated the area of atheromatous plaque and hepatic lipid accumulation. Compared with AS model group, wheat bran fiber decreased liver homogenate TC level((60. 56±13. 49) µmol/g vs. (51. 10±5. 94) µmol/g)(P<0. 05), reduced protein expression of SREBP-1, FAS and ACC(P<0. 05), increased protein expression of SREBP-2SR-B1(P<0. 05). CONCLUSION: Taken together, wheat bran fiber can delay the occurance of AS by regulating the related protein expressions involved in lipid metabolism and improving hepatic lipid metabolism.


Assuntos
Fibras na Dieta , Metabolismo dos Lipídeos , Animais , Apolipoproteínas E , Dieta Hiperlipídica , Fígado , Masculino , Camundongos , Proteína de Ligação a Elemento Regulador de Esterol 1 , Triglicerídeos , Triticum
9.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3780-3785, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602953

RESUMO

The aim of this paper was to investigate the molecular mechanism of Calculus Bovis Sativus( CBS) in alleviating lipid accumulation in vitro by serum pharmacology. The CBS-containing serum of mice was obtained by serum pharmacology method to evaluate its effect on the proliferation of LO2 hepatocytes. The lipid reducing effects of CBS-containing serum through Nrf2 was evaluated by fructose-induced LO2 hepatocyte steatosis model,nuclear factor erythroid 2 related factor 2( Nrf2) agonist oltipraz combined intervention,cell oil red O staining and intracellular triglyceride( TG) content. The effects of CBS-containing serum on lipid peroxidation and hepatocytes apoptosis were evaluated by reactive oxygen species( ROS) and apoptosis assay,respectively. Real-time quantitative polymerase chain reaction( PCR) was used to detect the relative expression of lipid synthesis-related genes and apoptosis-related genes.RESULTS:: showed that CBS drug-containing serum had no significant effect on LO2 hepatocyte proliferation. As compared with the model group,CBS-containing serum could effectively reduce the formation of lipid droplets in fructose-induced LO2 hepatocytes,significantly reduce intracellular TG and ROS levels,and significantly reduce hepatocyte apoptosis rate( P < 0. 05). As compared with the model group,carbohydrate responsive element binding protein( ChREBP),sterol regulatory element binding protein-1 c( SREBP-1 c),fatty acid synthase( FAS),acetyl-CoA carboxylase 1( ACC1),stearoyl-CoA desaturase 1( SCD1),Bax and caspase-3 mRNA levels were significantly reduced in CBS drug-containing serum treatment group( P<0. 05). All of the above effects could be reversed by oltipraz.In conclusion,CBS-containing serum can significantly inhibit the fructose-induced LO2 liver fat deposition,and the mechanism may be related to reducing intracellular ROS level through the Nrf2 pathway and improving intracellular peroxidation state to reduce apoptosis.


Assuntos
Cálculos Biliares/química , Hepatócitos/citologia , Soro/química , Animais , Apoptose , Bovinos , Células Cultivadas , Fígado Gorduroso , Frutose , Hepatócitos/metabolismo , Metabolismo dos Lipídeos , Peroxidação de Lipídeos , Fígado , Medicina Tradicional Chinesa , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos
10.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3798-3805, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602956

RESUMO

Based on metabolomics,the metabolites of larvae zebrafish with overdose of Panax notoginseng saponins( PNS) were compared with those in normal group of larvae zebrafish to investigate the possible toxicity mechanism of overdose PNS in larvae zebrafish. An experimental animal model of long-term toxicity induced by PNS overdose was established by administering 1-6 dpf at low,medium and high doses of PNS,respectively. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry( UPLC-Q-TOF-MS) technique was combined with principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA) to screen and identify biomarkers associated with toxicity,and then the MetaboAnalyst database was used to analyze metabolism-related pathways. The results showed that the metabolites of each group could be distinguished distinctly,and they deviated more from the normal group in a time and dose dependent manner. Twenty-nine potential biomarkers related to toxicity( VIP>1,P<0. 05) were identified preliminarily,mainly involving six metabolic pathways. From the metabonomics point of view,the toxicity mechanism of overdose PNS may be related to the disorders of lipid metabolism,amino acid metabolism and energy metabolism.


Assuntos
Metabolômica , Panax notoginseng/toxicidade , Saponinas/toxicidade , Aminoácidos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Metabolismo Energético , Larva/efeitos dos fármacos , Metabolismo dos Lipídeos , Espectrometria de Massas , Testes de Toxicidade Aguda , Peixe-Zebra
11.
Phys Chem Chem Phys ; 21(41): 22679-22694, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31595905

RESUMO

Peptide misfolding and aberrant assembly in membranous micro-environments have been associated with numerous neurodegenerative diseases. The biomolecular mechanisms and biophysical implications of these amyloid membrane interactions have been under extensive research and can assist in understanding disease pathogenesis and potential development of rational therapeutics. But, the complex nature and diversity of biomolecular interactions, structural transitions, and dependence on local environmental conditions have made accurate microscopic characterization challenging. In this review, using cases of Alzheimer's disease (amyloid-beta peptide), Parkinson's disease (alpha-synuclein peptide) and Huntington's disease (huntingtin protein), we illustrate existing challenges in experimental investigations and summarize recent relevant numerical simulation studies into amyloidogenic peptide-membrane interactions. In addition we project directions for future in silico studies and discuss shortcomings of current computational approaches.


Assuntos
Biologia Computacional , Lipídeos/química , Doenças Neurodegenerativas , Dobramento de Proteína , Proteínas Amiloidogênicas/metabolismo , Membrana Celular/metabolismo , Simulação por Computador , Humanos , Metabolismo dos Lipídeos , Doenças Neurodegenerativas/fisiopatologia , Peptídeos/metabolismo
12.
Nature ; 574(7777): 249-253, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31578523

RESUMO

The integrity of the mammalian epidermis depends on a balance of proliferation and differentiation in the resident population of stem cells1. The kinase RIPK4 and the transcription factor IRF6 are mutated in severe developmental syndromes in humans, and mice lacking these genes display epidermal hyperproliferation and soft-tissue fusions that result in neonatal lethality2-5. Our understanding of how these genes control epidermal differentiation is incomplete. Here we show that the role of RIPK4 in mouse development requires its kinase activity; that RIPK4 and IRF6 expressed in the epidermis regulate the same biological processes; and that the phosphorylation of IRF6 at Ser413 and Ser424 primes IRF6 for activation. Using RNA sequencing (RNA-seq), histone chromatin immunoprecipitation followed by sequencing (ChIP-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) of skin in wild-type and IRF6-deficient mouse embryos, we define the transcriptional programs that are regulated by IRF6 during epidermal differentiation. IRF6 was enriched at bivalent promoters, and IRF6 deficiency caused defective expression of genes that are involved in the metabolism of lipids and the formation of tight junctions. Accordingly, the lipid composition of the stratum corneum of Irf6-/- skin was abnormal, culminating in a severe defect in the function of the epidermal barrier. Collectively, our results explain how RIPK4 and IRF6 function to ensure the integrity of the epidermis and provide mechanistic insights into why developmental syndromes that are characterized by orofacial, skin and genital abnormalities result when this axis goes awry.


Assuntos
Diferenciação Celular , Células Epidérmicas/citologia , Epiderme/fisiologia , Fatores Reguladores de Interferon/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Anormalidades Múltiplas/genética , Animais , Fenda Labial/genética , Fissura Palatina/genética , Cistos/genética , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Células Epidérmicas/metabolismo , Epiderme/embriologia , Anormalidades do Olho/genética , Feminino , Dedos/anormalidades , Regulação da Expressão Gênica , Fatores Reguladores de Interferon/deficiência , Fatores Reguladores de Interferon/genética , Joelho/anormalidades , Articulação do Joelho/anormalidades , Lábio/anormalidades , Metabolismo dos Lipídeos/genética , Deformidades Congênitas das Extremidades Inferiores/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Fosfosserina/metabolismo , Proteínas Serina-Treonina Quinases/genética , Sindactilia/genética , Anormalidades Urogenitais/genética
13.
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
14.
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
15.
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
16.
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
17.
Life Sci ; 235: 116834, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31493478

RESUMO

Obesity has a positive relation to non-alcoholic fatty liver disease (NAFLD) and studies have demonstrated that strength training can regulate lipid accumulation in the hepatocytes of obese rats. AIMS: Our aim is to evaluate the effects of high fat diet and strength training on markers of oxidation and lipogenesis in the liver of Wistar rats. MAIN METHODS: Forty Wistar rats were divided into four groups (n = 10): control (CTL), strength training (TR), high fat diet consumption (HF) and high fat diet consumption with strength training (HFT). Animals were subjected to physical strength training and high fat diet consumption for 12 weeks, 3 session per week. Then, the animals were euthanized, and liver markers were evaluated via immunolabeling. KEY FINDINGS: Our results indicated that strength training reduced the expression of adiposity as well as the accumulation of glycogen and lipids in the liver. This reduction of fatty acid (FA) stored in hepatocytes is related to reduction of proteins linked to ß-oxidation such as Fas/CD95, LIMP-II and CD36, as well as other proteins linked to lipogeneses such as SREBP-1. SIGNIFICANCE: Finally, we observed that high fat diet can alter lipogenesis and reduce ß-oxidation promoted hepatic fat accumulation. In conclusion, there was a reduction of obesity-related hepatic lipogenesis after 12 weeks of strength training.


Assuntos
Metabolismo dos Lipídeos , Fígado/metabolismo , Obesidade/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glicogênio/metabolismo , Lipogênese , Masculino , Oxirredução , Proteínas/metabolismo , Ratos
18.
Nat Med ; 25(9): 1385-1389, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501613

RESUMO

The worldwide obesity epidemic1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived 14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.


Assuntos
Envelhecimento/metabolismo , Peso Corporal/genética , Obesidade/metabolismo , Ganho de Peso/genética , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adolescente , Adulto , Envelhecimento/genética , Envelhecimento/patologia , Peso Corporal/fisiologia , Radioisótopos de Carbono/química , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Masculino , Obesidade/genética , Obesidade/patologia , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/patologia , Triglicerídeos/metabolismo , Perda de Peso/genética
19.
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
20.
Endocrinology ; 160(10): 2339-2352, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504411

RESUMO

Osteoporosis is a complication of diabetes mellitus (DM). The pathology of diabetic osteoporosis is distinct from postmenopausal osteoporosis, and there are no specific treatment guidelines for diabetic osteoporosis. In the current study, this issue was addressed by evaluating the effect of osteoporosis medications, such as the anabolic agent PTH [teriparatide (TPTD)] and the antiresorptive agents calcitonin [elcatonin (ECT)] and bisphosphonate [risedronate (RIS)], on bone metabolism as well as on glucose and lipid metabolism in spontaneously diabetic Torii (SDT) fatty rats, which are a model of type 2 DM (T2DM). The medicines were injected subcutaneously into 8-week-old male SDT fatty rats three times weekly for 8 weeks. TPTD treatment in SDT fatty rats increased the osteoblast number and function on trabecular bone in vertebrae, and increased the trabecular bone mass, bone mineral density (BMD), and mechanical strength of vertebrae. Additionally, TPTD improved cortical bone structure and increased BMD. RIS decreased the osteoclast number and function, which led to an increase in vertebral bone mineral content and BMD in the femoral diaphysis, and mechanical strength was increased in the vertebrae. ECT showed no clear effects on bone mass or metabolism. Similar to diabetic lesions, all of the drugs had no effects on hyperglycemia, pancreas morphology, or serum insulin and glucagon levels. However, triglyceride levels and lipid droplets in fatty liver were decreased in the TPTD group. These results suggest that TPTD may be useful for treating fatty liver in addition to osteoporosis in T2DM.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Teriparatida/farmacologia , Animais , Glicemia , Densidade Óssea/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos
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