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Photobiomodulation, utilising non-ionising light in the visible and near-infrared (NIR) spectrum, has been suggested as a potential method for enhancing tissue repair, reducing inflammation and possibly mitigating cancer-therapy-associated side effects. NIR light is suggested to be absorbed intracellularly, mainly by chromophores within the mitochondria. This study examines the impact of 734 nm NIR light on cellular senescence. Cancer (MCF7 and A549) and non-cancer (MCF10A and IMR-90) cell populations were subjected to 63 mJ/cm2 NIR-light exposure for 6 days. Senescence levels were quantified by measuring active senescence-associated beta-galactosidase. Exposure to NIR light significantly increases senescence levels in cancer (10.0%-203.2%) but not in non-cancer cells (p > 0.05). Changes in senescence were associated with significant modulation of mitochondrial homeostasis, including increased levels of reactive oxygen species (p < 0.05) and mitochondrial membrane potential (p < 0.05) post-NIR-light treatment. These results suggest that NIR light modulates cellular chemistry, arresting the proliferation of cancer cells via senescence induction while sparing non-cancer cells.
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Senescência Celular , Raios Infravermelhos , Mitocôndrias , Humanos , Senescência Celular/efeitos da radiação , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos da radiação , Linhagem Celular TumoralRESUMO
BACKGROUND: Studies have linked daily pollen counts to respiratory allergic health outcomes, but few have considered allergen levels. OBJECTIVE: We sought to assess associations of grass pollen counts and grass allergen levels (Phl p 5) with respiratory allergic health symptoms in a panel of 93 adults with moderate-severe allergic rhinitis and daily asthma hospital admissions in London, United Kingdom. METHODS: Daily symptom and medication scores were collected from adult participants in an allergy clinical trial. Daily counts of asthma hospital admissions in the London general population were obtained from Hospital Episode Statistics data. Daily grass pollen counts were measured using a volumetric air sampler, and novel Phl p 5 levels were measured using a ChemVol High Volume Cascade Impactor and ELISA analyses (May through August). Associations between the 2 pollen variables and daily health scores (dichotomized based on within-person 75th percentiles) were assessed using generalized estimating equation logistic models and with asthma hospital admissions using Poisson regression models. RESULTS: Daily pollen counts and Phl p 5 levels were each positively associated with reporting a high combined symptom and medication health score in separate models. However, in mutually adjusted models including terms for both pollen counts and Phl p 5 levels, associations remained for Phl p 5 levels (odds ratio [95% CI]: 1.18 [1.12, 1.24]), but were heavily attenuated for pollen counts (odds ratio [95% CI]: 1.00 [0.93, 1.07]). Similar trends were not observed for asthma hospital admissions in London. CONCLUSIONS: Grass allergen (Phl p 5) levels are more consistently associated with allergic respiratory symptoms than grass pollen counts.
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Asma , Rinite Alérgica Sazonal , Rinite Alérgica , Adulto , Humanos , Rinite Alérgica Sazonal/epidemiologia , Pólen , Alérgenos , Poaceae , Asma/epidemiologia , Proteínas de Plantas/análiseRESUMO
AIMS: The presence of foodborne pathogens in preharvest agricultural water has been identified as a potential contamination source in outbreak investigations, driving markets and auditing bodies to begin requiring water treatment for high-risk produce. Therefore, it is essential that we identify water treatment methods which are effective as well as practical in their application on farm. METHODS AND RESULTS: In this work, we evaluated two sanitizers which are most prominent in preharvest agricultural water treatment (calcium hypochlorite (free chlorine: 3-5 ppm) and peracetic acid (PAA: 5 ppm)), an EPA registered antimicrobial device (ultraviolet light (UV)), in addition to a combination approach (chlorine + UV, PAA + UV). Treatments were evaluated for their ability to inactivate total coliforms and generic Escherichia coli and consistency in treatment efficacy over 1 h of operation. Physicochemical variables were measured along with microbial populations at 0, 5, 15, 30, 45 and 60 min of operation. Escherichia coli and coliform counts showed a significant (P < 0·05) reduction after treatment, with combination and singular treatments equally effective at inactivating E. coli and coliforms. A significant increase (P < 0·05) in oxidation-reduction potential was seen during water treatment (Chlorine; UV + Chlorine), and a significant reduction (P < 0·05) in pH was seen after PAA and PAA + UV treatments (60 min). CONCLUSION: Overall, the results indicate that all treatments evaluated are equally efficacious for inactivating E. coli and coliforms present in surface agricultural water. SIGNIFICANCE AND IMPACT OF THE STUDY: This information when paired with challenge studies targeting foodborne pathogens of interest can be used to support grower decisions when selecting and validating a preharvest agricultural water treatment programme.
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Irrigação Agrícola , Desinfetantes , Contaminação de Alimentos/prevenção & controle , Purificação da Água , Compostos de Cálcio/farmacologia , Cloro/farmacologia , Contagem de Colônia Microbiana , Desinfetantes/farmacologia , Escherichia coli , Microbiologia de Alimentos , Ácido Peracético/farmacologiaRESUMO
Several concepts for platinum-based catalysts for the oxygen reduction reaction (ORR) are presented that exceed the US Department of Energy targets for Pt-related ORR mass activity. Most concepts achieve their high ORR activity by increasing the Pt specific activity at the expense of a lower electrochemically active surface area (ECSA). In the potential region controlled by kinetics, such a lower ECSA is counterbalanced by the high specific activity. At higher overpotentials, however, which are often applied in real systems, a low ECSA leads to limitations in the reaction rate not by kinetics, but by mass transport. Here we report on self-supported platinum-cobalt oxide networks that combine a high specific activity with a high ECSA. The high ECSA is achieved by a platinum-cobalt oxide bone nanostructure that exhibits unprecedentedly high mass activity for self-supported ORR catalysts. This concept promises a stable fuel-cell operation at high temperature, high current density and low humidification.
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Microplastics have been observed in indoor and outdoor air. This raises concern for human exposure, especially should they occur in small enough sizes, which if inhaled, reach the central airway and distal lung. As yet, methods for their detection have not spectroscopically verified the chemical composition of microplastics in this size-range. One proposed method is an automated spectroscopic technique, Raman spectral imaging; however, this generates large and complex data sets. This study aims to optimize Raman spectral imaging for the identification of microplastics (≥2 µm) in ambient particulate matter, using different chemometric techniques. We show that Raman spectral images analyzed using chemometric statistical approaches are appropriate for the identification of both virgin and environmental microplastics ≥2 µm in size. On the basis of the sensitivity, we recommend using the developed Pearson's correlation and agglomerative hierarchical cluster analysis for the identification of microplastics in spectral data sets. Finally, we show their applicability by identifying airborne microplastics >4.7 µm in an outdoor particulate matter sample obtained at an urban sampling site in London, United Kingdom. This semiquantitative method will enable the procurement of exposure concentrations of airborne microplastics guiding future toxicological assessments.
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Microplásticos/análise , Material Particulado/análise , Análise Espectral Raman/métodos , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Poliestirenos/químicaRESUMO
Tropical peatlands hold about 15%-19% of the global peat carbon (C) pool of which 77% is stored in the peat swamp forests (PSFs) of Southeast Asia. Nonetheless, these PSFs have been drained, exploited for timber and land for agriculture, leading to frequent fires in the region. The physico-chemical characteristics of peat, as well as the hydrology of PSFs are affected after a fire, during which the ecosystem can act as a C source for decades, as C emissions to the atmosphere exceed photosynthesis. In this work, we studied the longer-term impact of fires on C cycling in tropical PSFs, hence we quantified the magnitude and patterns of C loss (CO2 , CH4 and dissolved organic carbon) and soil-water quality characteristics in an intact and a degraded burnt PSF in Brunei Darussalam affected by seven fires over the last 40 years. We used natural tracers such as 14 C to investigate the age and sources of C contributing to ecosystem respiration (Reco ) and CH4 , while we continuously monitored soil temperature and water table (WT) level from June 2017 to January 2019. Our results showed a major difference in the physico-chemical parameters, which in turn affected C dynamics, especially CH4 . Methane effluxes were higher in fire-affected areas (7.8 ± 2.2 mg CH4 m-2 hr-1 ) compared to the intact PSF (4.0 ± 2.0 mg CH4 m-2 hr-1 ) due to prolonged higher WT and more optimal methanogenesis conditions. On the other hand, we did not find significant differences in Reco between burnt (432 ± 83 mg CO2 m-2 hr-1 ) and intact PSF (359 ± 76 mg CO2 m-2 hr-1 ). Radiocarbon analysis showed overall no significant difference between intact and burnt PSF with a modern signature for both CO2 and CH4 fluxes implying a microbial preference for the more labile C fraction in the peat matrix.
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Solo , Áreas Alagadas , Sudeste Asiático , Brunei , Carbono , Dióxido de Carbono/análise , Ecossistema , Florestas , Metano/análiseRESUMO
Type 2 diabetes is more common in non-Europeans and starts at a younger age and at lower BMI cut-offs. This review discusses the insights from genetic studies about pathophysiological mechanisms which determine risk of disease with a focus on the role of adiposity and body fat distribution in ethnic disparity in risk of type 2 diabetes. During the past decade, genome-wide association studies (GWAS) have identified more than 400 genetic variants associated with the risk of type 2 diabetes. The Eurocentric nature of these genetic studies has made them less effective in identifying mechanisms that make non-Europeans more susceptible to higher risk of disease. One possible mechanism suggested by epidemiological studies is the role of ethnic difference in body fat distribution. Using genetic variants associated with an ability to store extra fat in a safe place, which is subcutaneous adipose tissue, we discuss how different ethnic groups could be genetically less susceptible to type 2 diabetes by developing a more favourable fat distribution.
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Adiposidade/etnologia , Diabetes Mellitus Tipo 2/etnologia , Obesidade/etnologia , Tecido Adiposo/diagnóstico por imagem , Adiposidade/genética , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Imageamento por Ressonância Magnética , Obesidade/genética , Relação Cintura-QuadrilRESUMO
PURPOSE: Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender. METHODS: MR data were acquired on a 1.5 T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multiparametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25 kg/m2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk. RESULTS: The cT1 values in the low-risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643 to 694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values. CONCLUSION: The majority of cT1 values are tightly clustered in a population at low risk for NAFL, suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease.
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Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Adulto , Idoso , Bancos de Espécimes Biológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Reino UnidoRESUMO
Exosomes and microvesicles (EMV) are lipid bilayer-enclosed structures, released by cells and involved in intercellular communication through transfer of proteins and genetic material. EMV release is also associated with various pathologies, including cancer, where increased EMV release is amongst other associated with chemo-resistance and active transfer of pro-oncogenic factors. Recent studies show that EMV-inhibiting agents can sensitize cancer cells to chemotherapeutic agents and reduce cancer growth in vivo. Cannabidiol (CBD), a phytocannabinoid derived from Cannabis sativa, has anti-inflammatory and anti-oxidant properties, and displays anti-proliferative activity. Here we report a novel role for CBD as a potent inhibitor of EMV release from three cancer cell lines: prostate cancer (PC3), hepatocellular carcinoma (HEPG2) and breast adenocarcinoma (MDA-MB-231). CBD significantly reduced exosome release in all three cancer cell lines, and also significantly, albeit more variably, inhibited microvesicle release. The EMV modulating effects of CBD were found to be dose dependent (1 and 5 µM) and cancer cell type specific. Moreover, we provide evidence that this may be associated with changes in mitochondrial function, including modulation of STAT3 and prohibitin expression, and that CBD can be used to sensitize cancer cells to chemotherapy. We suggest that the known anti-cancer effects of CBD may partly be due to the regulatory effects on EMV biogenesis, and thus CBD poses as a novel and safe modulator of EMV-mediated pathological events.
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CONTEXT: Randomized controlled trials in nonalcoholic fatty liver disease (NAFLD) have shown that regular exercise, even without calorie restriction, reduces liver steatosis. A previous study has shown that 16 weeks of supervised exercise training in NAFLD did not affect total very low-density lipoprotein (VLDL) kinetics. OBJECTIVE: The objective of the study was to determine the effect of exercise training on intrahepatocellular fat (IHCL) and the kinetics of large triglyceride (TG)-rich VLDL1 and smaller denser VLDL2, which has a lower TG content. DESIGN: This was a 16-week randomized controlled trial. PATIENTS: A total of 27 sedentary patients with NAFLD participated in the trial. INTERVENTION: The intervention was composed of supervised exercise with moderate-intensity aerobic exercise or conventional lifestyle advice (control). MAIN OUTCOME: VLDL1 and VLDL2-TG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes before and after the intervention. RESULTS: In the exercise group, maximal oxygen uptake increased by 31% ± 6% (mean ± SEM) and IHCL decreased from 19.6% (14.8%, 30.0%) to 8.9% (5.4%, 17.3%) (median [interquartile range]) with no significant change in maximal oxygen uptake or IHCL in the control group (change between groups, P < .001 and P = .02, respectively). Exercise training increased VLDL1-TG and apoB fractional catabolic rates, a measure of clearance, (change between groups, P = .02 and P = .01, respectively), and VLDL1-apoB production rate (change between groups, P = .006), with no change in VLDL1-TG production rate. Plasma TG did not change in either group. CONCLUSION: An increased clearance of VLDL1 may contribute to the significant decrease in liver fat after 16 weeks of exercise in NAFLD. A longer duration or higher-intensity exercise interventions may be needed to lower the plasma TG and VLDL production rate.
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Apolipoproteínas B/metabolismo , Terapia por Exercício/métodos , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/terapia , Avaliação de Resultados em Cuidados de Saúde , Adiposidade , Apolipoproteínas B/sangue , Humanos , Cinética , Lipoproteínas VLDL/sangue , Masculino , Pessoa de Meia-Idade , Comportamento Sedentário , Triglicerídeos/sangue , Triglicerídeos/metabolismoRESUMO
BACKGROUND/OBJECTIVES: Short-chain fatty acids, produced by microbiome fermentation of carbohydrates, have been linked to a reduction in appetite, body weight and adiposity. However, determining the contribution of central and peripheral mechanisms to these effects has not been possible. SUBJECTS/METHODS: C57BL/6 mice fed with either normal or high-fat diet were treated with nanoparticle-delivered acetate, and the effects on metabolism were investigated. RESULTS: In the liver, acetate decreased lipid accumulation and improved hepatic function, as well as increasing mitochondrial efficiency. In white adipose tissue, it inhibited lipolysis and induced 'browning', increasing thermogenic capacity that led to a reduction in body adiposity. CONCLUSIONS: This study provides novel insights into the peripheral mechanism of action of acetate, independent of central action, including 'browning' and enhancement of hepatic mitochondrial function.
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Ácido Acético/química , Adipócitos Marrons/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Ácidos Graxos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Adipócitos Marrons/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Modelos Animais de Doenças , Ácidos Graxos/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacosRESUMO
Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy.
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Tecido Adiposo/patologia , Hepatócitos/metabolismo , Fenômenos Fisiológicos da Nutrição do Lactente , Metabolismo dos Lipídeos , Lipídeos/sangue , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Pré-Natal , Caracteres Sexuais , Adiposidade , Feminino , Humanos , Lactente , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate the association between objectively measured sitting and standing, using a postural allocation technique, with MRI-assessed body composition. DESIGN: The present study was a cross-sectional pilot study. SETTING: Participants were examined at one centre located in London, UK. PARTICIPANTS: Normal weight Caucasian women (30.9±6.1â years; body mass index (BMI), 22.9±3.4â kg/m(2)) with desk-bound occupations were recruited to minimise variability in body composition outcomes. A convenience sample of 12 women was recruited in January 2014 from University College London. OUTCOME MEASURES: For each participant a number of body composition variables were attained from a single whole-body MRI session. Main outcome variables included: total and liver adiposity, visceral/subcutaneous fat ratio and BMI. Main exposure variables included: average sitting time, standing:sitting ratio and step count. Pearson correlations were carried out to examine associations between different activity categories and body composition variables. RESULTS: There were significant correlations between average daily sitting and liver adiposity and visceral/subcutaneous abdominal fat ratio (r=0.66 and 0.64, respectively); standing:sitting ratio was moderately correlated with liver adiposity and visceral/subcutaneous abdominal fat ratio (r=-0.53 and -0.45); average daily step count was moderately correlated with liver adiposity, total adiposity and visceral/subcutaneous abdominal fat ratio (r=-0.45, -0.46 and -0.51, respectively). CONCLUSIONS: This pilot study has provided preliminary evidence of relationships between objectively measured sitting and standing and precise measures of body composition.
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Composição Corporal , Imageamento por Ressonância Magnética , Postura , Adiposidade , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal , Pessoa de Meia-Idade , Projetos Piloto , Adulto JovemRESUMO
Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2âmmol/mol) consumed, in a random order, either 40âg of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.
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Obesity and its co-morbidities, including type II diabetes, insulin resistance and cardiovascular diseases, have become one of the biggest health issues of present times. The impact of obesity goes well beyond the individual and is so far-reaching that, if it continues unabated, it will cause havoc with the economies of most countries. In order to be able to fully understand the relationship between increased adiposity (obesity) and its co-morbidity, it has been necessary to develop proper methodology to accurately and reproducibly determine both body fat content and distribution, including ectopic fat depots. Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) have recently emerged as the gold-standard for accomplishing this task. Here, we will review the use of different MRI techniques currently being used to determine body fat content and distribution. We also discuss the pros and cons of MRS to determine ectopic fat depots in liver, muscle, pancreas and heart and compare these to emerging MRI techniques currently being put forward to create ectopic fat maps. Finally, we will discuss how MRI/MRS techniques are helping in changing the perception of what is healthy and what is normal and desirable body-fat content and distribution.
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Tecido Adiposo/patologia , Resistência à Insulina , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Obesidade/patologia , Tecido Adiposo/metabolismo , Humanos , Obesidade/metabolismoRESUMO
AIMS/HYPOTHESIS: We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. METHODS: We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. RESULTS: pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis. CONCLUSIONS/INTERPRETATION: pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.
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Diabetes Gestacional/metabolismo , Insulina/metabolismo , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Adulto , Diabetes Mellitus Tipo 2/metabolismo , Fígado Gorduroso/metabolismo , Feminino , Humanos , Resistência à Insulina/fisiologia , Hepatopatia Gordurosa não Alcoólica , GravidezRESUMO
BACKGROUND: We have previously shown that by term age, preterm infants have elevated intrahepatocellular lipid (IHCL) content and altered regional adiposity, both of which are risk factors for cardiometabolic illness in adult life. Preterm nutritional intake is a plausible determinant of these aberrant trajectories of development. OBJECTIVE: We aimed to establish if macronutritional components of the preterm diet were determinants of IHCL deposition measured at term equivalent age, using (1)H Magnetic Resonance spectroscopy (MRS). METHODS: Prospective observational case-control study in a single UK neonatal unit. (1)H MR spectra were acquired from 18 preterm infants (<32 weeks gestational age at birth) at term age and 31 healthy term infants, who acted as a control group. Neonatal nutritional information was collected from birth to 34(+6) weeks postmenstrual age. RESULTS: IHCL (median, interquartile range) was significantly higher in preterm-at-term infants compared with term-born infants: 0.735, 0-1.46 versus 0.138, 0-0.58; P=0.003. In preterm infants, IHCL was positively correlated with lipid intake in the first week of life (r=0.52, P=0.04). CONCLUSIONS: This study confirms our previous observation of elevated IHCL in preterm infants at term and suggests that early lipid intake may be a determinant. Future work is warranted to establish the clinical relevance and the role of nutritional intervention in attenuating or exacerbating this effect in preterm infants.
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Adiposidade , Hepatócitos/metabolismo , Recém-Nascido Prematuro/metabolismo , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Metabolismo dos Lipídeos , Espectroscopia de Ressonância Magnética , Masculino , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Estudos Prospectivos , Reino UnidoRESUMO
BACKGROUND/OBJECTIVES: It is well established that combining a reduced calorie, low-fat diet with the lipase inhibitor orlistat results in significantly greater weight loss than placebo plus diet. This weight loss is accompanied by changes in adipose tissue (AT) distribution. As 60 mg orlistat is now available as an over-the-counter medication, the primary objective of this study was to determine whether 60 mg orlistat is effective as a weight loss option in a free-living community population with minimal professional input. METHODS: AT and ectopic lipid content were measured using magnetic resonance imaging and (1)H MR spectroscopy, respectively, in 27 subjects following 3 months treatment with orlistat 60 mg and a reduced calorie, low-fat diet. RESULTS: Significant reductions in intra-abdominal AT (-10.6%, P=0.023), subcutaneous (-11.7% P<0.0001) and pericardial fat (-9.8%, P=0.034) volumes and intrahepatocellular lipids (-43.3%, P=0.0003) were observed. These changes in body fat content and distribution were accompanied by improvements in plasma lipids and decreases in blood pressure and heart rate. CONCLUSION: These findings suggest that over-the-counter 60 mg orlistat, in combination with the type of advice a subject could expect to be given when obtaining 60 mg orlistat in a community setting, does indeed result in potentially clinically beneficial changes in body composition and risk factors for metabolic diseases.
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Fármacos Antiobesidade/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Lactonas/uso terapêutico , Lipase/antagonistas & inibidores , Medicamentos sem Prescrição/uso terapêutico , Obesidade Abdominal/tratamento farmacológico , Gordura Abdominal/efeitos dos fármacos , Gordura Abdominal/patologia , Adiposidade/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/administração & dosagem , Índice de Massa Corporal , Terapia Combinada , Dieta com Restrição de Gorduras , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Lactonas/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Medicamentos sem Prescrição/administração & dosagem , Obesidade Abdominal/sangue , Obesidade Abdominal/dietoterapia , Obesidade Abdominal/patologia , Orlistate , Sobrepeso/sangue , Sobrepeso/dietoterapia , Sobrepeso/tratamento farmacológico , Sobrepeso/patologia , Redução de Peso/efeitos dos fármacos , Adulto JovemRESUMO
AIMS: Diets rich in non-viscous fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. This study was undertaken to assess whether chronic consumption of this type of fibre in individuals with the metabolic syndrome would improve insulin sensitivity via changes in ectopic fat storage. METHODS: The study was a single-blind, randomized, parallel nutritional intervention where 20 insulin resistant subjects consumed either the fibre supplement (resistant starch) (40 g/day) or placebo supplement (0 g/day) for 12 weeks. Insulin sensitivity was measured by euglycaemic-hyperinsulinaemic clamp and ectopic fat storage measured by whole-body magnetic resonance spectroscopy. RESULTS: Resistant starch consumption did not significantly affect body weight, fat storage in muscle, liver or visceral depots. There was also no change with resistant starch feeding on vascular function or markers of inflammation. However, in subjects randomized to consume the resistant starch, insulin sensitivity improved compared with the placebo group (P = 0.023). Insulin sensitivity correlated significantly with changes in waist circumference and fat storage in tibialis muscle and to a lesser extent to visceral-to-subcutaneous abdominal adipose tissue ratio. CONCLUSION: Consumption of resistant starch improves insulin sensitivity in subjects with the metabolic syndrome. Unlike in animal models, diabetes prevention does not appear to be directly related to changes in body adiposity, blood lipids or inflammatory markers. Further research to elucidate the mechanisms behind this change in insulin sensitivity in human subjects is required.