Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Am J Physiol Endocrinol Metab ; 324(2): E176-E184, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36629822

RESUMEN

Sarcopenia, the age-related loss of skeletal muscle mass, is associated with lipid accumulation and anabolic resistance; phenomena also observed in obesity and worsen when obesity and aging are combined. The endocannabinoid system (ECS) is overactivated in obesity, but its role in aging obesity-related muscle dysfunction is unknown. The aims of this study were to evaluate the effect of inhibition of the ECS by rimonabant (RIM) on the metabolic alterations induced by a high-fat high-sucrose diet and on skeletal muscle mass/function in aged mice. Eighteen-month-old male mice were subjected to a control (CTL) or a high-fat high-sucrose (HFHS) diet for 24 weeks. Mice were administered with saline or RIM (10 mg/kg/day) for the last 4 weeks of the diet. Skeletal muscle function was evaluated by open-field, rotarod, and grip strength tests. Metabolic alterations in liver, adipose tissue, and skeletal muscle were investigated by quantitative RT-PCR. Body mass was higher in HFHS mice compared to CTL mice (48.0 ± 1.5 vs. 33.5 ± 0.7 g, P < 0.01), as a result of fat accumulation (34.8 ± 1.0 vs. 16.7 ± 0.8%, P < 0.01). RIM reduced body fat mass in both CTL (-16%, P < 0.05) and HFHS conditions (-40%, P < 0.01), without affecting hindlimb skeletal muscle mass. In HFHS mice, grip strength evolution was improved (-0.29 ± 0.06 vs. -0.49 ± 0.06 g/g lean mass, P < 0.05), and rotarod activity was increased by ≈60% in response to RIM (45.9 ± 6.3 vs. 28.5 ± 4.6 cm, P < 0.05). Lipolysis and ß-oxidation genes were upregulated in the liver as well as genes involved in adipose tissue browning. These results demonstrate that inhibition of the ECS induces metabolic changes in liver and adipose tissue associated with a reversion of the obese phenotype and that RIM is able to improve motor coordination and muscle strength in aged mice, without affecting skeletal muscle mass.NEW & NOTEWORTHY In 24-month-old mice submitted to high-fat high-sucrose-induced obesity, inhibition of the endocannabinoid system by rimonabant reversed the obese phenotype by promoting adipose tissue browning and ß-oxidation in the liver but not in skeletal muscle. These metabolism modifications are associated with improved skeletal muscle function.


Asunto(s)
Endocannabinoides , Obesidad , Masculino , Animales , Ratones , Endocannabinoides/metabolismo , Rimonabant/farmacología , Obesidad/metabolismo , Músculo Esquelético/metabolismo , Dieta Alta en Grasa , Fenotipo , Sacarosa/farmacología , Ratones Endogámicos C57BL
2.
Am J Physiol Endocrinol Metab ; 321(3): E325-E337, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34250814

RESUMEN

The number of older obese adults is increasing worldwide. Whether obese adults show similar health benefits in response to lifestyle interventions at different ages is unknown. The study enrolled 25 obese men (body mass index: 31-39 kg/m2) in two arms according to age (30-40 and 60-70 yr old). Participants underwent an 8-wk intervention with moderate calorie restriction (∼20% below individual energy requirements) and supervised endurance training resulting in ∼5% weight loss. Body composition was measured using dual energy X-ray absorptiometry. Insulin sensitivity was assessed during a hypersinsulinemic-euglycemic clamp. Cardiometabolic profile was derived from blood parameters. Subcutaneous fat and vastus lateralis muscle biopsies were used for ex vivo analyses. Two-way repeated-measure ANOVA and linear mixed models were used to evaluate the response to lifestyle intervention and comparison between the two groups. Fat mass was decreased and bone mass was preserved in the two groups after intervention. Muscle mass decreased significantly in older obese men. Cardiovascular risk (Framingham risk score, plasma triglyceride, and cholesterol) and insulin sensitivity were greatly improved to a similar extent in the two age groups after intervention. Changes in adipose tissue and skeletal muscle transcriptomes were marginal. Analysis of the differential response to the lifestyle intervention showed tenuous differences between age groups. These data suggest that lifestyle intervention combining calorie restriction and exercise shows similar beneficial effects on cardiometabolic risk and insulin sensitivity in younger and older obese men. However, attention must be paid to potential loss of muscle mass in response to weight loss in older obese men.NEW & NOTEWORTHY Rise in obesity and aging worldwide are major trends of critical importance in public health. This study addresses a current challenge in obesity management. Do older obese adults respond differently to a lifestyle intervention composed of moderate calorie restriction and supervised physical activity than younger ones? The main conclusion of the study is that older and younger obese men similarly benefit from the intervention in terms of cardiometabolic risk.


Asunto(s)
Adaptación Fisiológica , Sistema Cardiovascular/metabolismo , Estilo de Vida , Obesidad/metabolismo , Programas de Reducción de Peso , Adulto , Factores de Edad , Anciano , Composición Corporal , Humanos , Masculino , Persona de Mediana Edad
3.
Curr Opin Lipidol ; 31(1): 8-14, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31815756

RESUMEN

PURPOSE OF REVIEW: To focus on state-of-the-art knowledge on the apolipoprotein M (ApoM) physiology and physiopathology regarding metabolism. RECENT FINDINGS: In humans, the ApoM was recently described as secreted by adipocytes. Obesity, metabolic syndrome and type 2 diabetes are associated with low circulating ApoM and adipose tissue APOM expression. Dieting-induced weight loss enhances adipose tissue expression and secretion, and exercise training increases plasma ApoM. The ApoM is a chaperone for the bioactive sphingolipid, sphingosine-1-phosphate (S1P), which has a specific role in inflammation. Its association with S1P in the inhibition of brown adipose tissue activity and subsequent insulin sensitivity was reported with the model of ApoM-deficient mouse. SUMMARY: The adipose tissue is an endocrine organ responsible for obesity-related comorbidities. Obesity and dieting impact the adipose tissue secretory profile. The recent demonstration of ApoM being secreted by healthy adipocytes questions about the possible role of this adipose production in metabolic diseases. Low-circulating ApoM is associated with unhealthy metabolic phenotype. The lower circulating apoM during metabolic syndrome might be a cause of obesity-related comorbidities. Lifestyle interventions enhance ApoM production. Whether it acts in combination to S1P or other small lipidic molecules deserves further investigations.


Asunto(s)
Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Síndrome Metabólico/metabolismo , Tejido Adiposo/patología , Animales , Diabetes Mellitus Tipo 2/patología , Humanos , Síndrome Metabólico/etiología , Síndrome Metabólico/patología
4.
PLoS Biol ; 11(2): e1001485, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23431266

RESUMEN

When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.


Asunto(s)
Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Adolescente , Adulto , Anciano , Animales , Glucosa , Humanos , Lipólisis/efectos de los fármacos , Masculino , Ratones , Persona de Mediana Edad , Niacina/farmacología , Esterol Esterasa/metabolismo , Adulto Joven
5.
PLoS Comput Biol ; 11(1): e1004047, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25590576

RESUMEN

Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.


Asunto(s)
Tejido Adiposo/metabolismo , Restricción Calórica , Redes Reguladoras de Genes/genética , Obesidad/metabolismo , Pérdida de Peso/genética , Pérdida de Peso/fisiología , Adulto , Femenino , Perfilación de la Expresión Génica , Humanos , Persona de Mediana Edad , Adulto Joven
6.
Org Biomol Chem ; 14(38): 9012-20, 2016 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-27603797

RESUMEN

An efficient regiospecific total synthesis of several branched fatty acyl hydroxyl-fatty acids (FAHFA) has been achieved from available terminal alkenes and alkynes. The key steps feature a boron trifluoride mediated epoxide ring opening with acetylide carbanions, followed by hydrogenation of the alkyne function. The carboxylic acid of the hydroxylated chains is introduced at the last step of the synthesis to allow the esterification of the branched hydroxyl group by fatty acids beforehand. The chemical syntheses of a "linear" FAHFA and a branched FAHFA analog containing a Z-olefin in the hydroxyl-fatty acid chain are also reported. A LC-MS/MS method has been developed. Several reversed phase columns were compared. Regioisomers were separated.

7.
Diabetologia ; 58(11): 2627-36, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26245186

RESUMEN

AIMS/HYPOTHESIS: Activation of macrophages by fatty acids (FAs) is a potential mechanism linking obesity to adipose tissue (AT) inflammation and insulin resistance. Here, we investigated the effects of FAs released during adipocyte lipolysis on AT macrophages (ATMs). METHODS: Human THP-1 macrophages were treated with media from human multipotent adipose-derived stem (hMADS) adipocytes stimulated with lipolytic drugs. Macrophages were also treated with mixtures of FAs and an inhibitor of Toll-like receptor 4, since this receptor is activated by saturated FAs. Levels of mRNA and the secretion of inflammation-related molecules were measured in macrophages. FA composition was determined in adipocytes, conditioned media and macrophages. The effect of chronic inhibition or acute activation of fat cell lipolysis on ATM response was investigated in vivo in mice. RESULTS: Whereas palmitic acid alone activates THP-1, conditioned media from hMADS adipocyte lipolysis had no effect on IL, chemokine and cytokine gene expression, and secretion by macrophages. Mixtures of FAs representing de novo lipogenesis or habitual dietary conditions also had no effect. FAs derived from adipocyte lipolysis were taken up by macrophages and stored as triacylglycerol droplets. In vivo, chronic treatment with an antilipolytic drug did not modify gene expression and number of ATMs in mice with intact or defective Tlr4. Stimulation of adipocyte lipolysis increased storage of neutral lipids by macrophages without change in number and phenotype. CONCLUSIONS/INTERPRETATION: Our data suggest that adipocyte lipolysis does not activate inflammatory pathways in ATMs, which instead may act as scavengers of FAs.


Asunto(s)
Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Ácidos Grasos/metabolismo , Lipólisis/fisiología , Macrófagos/metabolismo , Triglicéridos/metabolismo , Adipocitos/citología , Tejido Adiposo/citología , Agonistas de Receptores Adrenérgicos beta 3/farmacología , Animales , Línea Celular , Dioxoles/farmacología , Ácidos Grasos/farmacología , Humanos , Inflamación/metabolismo , Macrófagos/citología , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Noqueados , Ácido Palmítico/farmacología , Células Madre/citología , Células Madre/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo
8.
Artículo en Inglés | MEDLINE | ID: mdl-37879623

RESUMEN

Understanding the relationship between blood nutrients and neurodegeneration could contribute to devising strategies for preventing Alzheimer's disease. We investigated the associations between fatty acids, vitamins D, B6, B12, folate, homocysteine, and the cerebral load of amyloid ß (Aß). This cross-sectional study included 177 older adults (70-96 years, 65% female) with objective cognitive impairment, prefrail, or frail. Cerebral Aß load was determined using positron emission tomography Standardized Uptake Value ratios. Fatty acids were assessed in erythrocytes, vitamins D and homocysteine in serum, and the other vitamins in plasma. Linear regression models corrected for multiple comparisons evaluated the associations between each nutrient and Aß. The principal component factor followed by linear regression grouped the fatty acids strongly correlated (factor) and associated with Aß. Higher concentrations of polyunsaturated fatty acids (PUFAs): clupanodonic acid (22:5n-3; ß: -0.13; p = .001), mead acid (20:3n-9; ß: -0.07; p = .036), and adrenic acid (22:4n-6; ß: -0.05; p = .031) were associated with lower global Aß load, whereas linoleic acid (18:2n-6) was associated with higher global Aß load (ß: 0.18; p = .042). Clupanodonic acid was inversely associated with Aß in all cerebral regions except the thalamus. The factor composed of mead, clupanodonic, and arachidonic (20:4n-6) acids was associated with a lower global Aß load (ß: -0.02; p = .002). Some erythrocyte PUFAs were inversely associated with Aß load in the brain, and most of them were metabolites of the essential fatty acids linoleic and α-linolenic. Given the cross-sectional design, these results must be carefully interpreted, and longitudinal studies are needed.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Anciano , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Biomarcadores , Estudios de Cohortes , Estudios Transversales , Ácidos Grasos/metabolismo , Homocisteína , Tomografía de Emisión de Positrones , Vitaminas
9.
Int J Vitam Nutr Res ; 83(6): 325-34, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-25497776

RESUMEN

OBJECTIVES: Oxidative stress is associated with the condition of cystic fibrosis (CF), but no guidelines exist for its assessment or treatment. Our aim was to evaluate a test that measures the blood antioxidant capability in CF children. METHODS: This antioxidant capability was assessed by the Kit Radicaux Libres (KRL) test in 44 CF children (24 boys). We recorded also anthropometric measures, pulmonary function, CF severity scores, and plasma nutritional and inflammatory parameters (proteins, vitamins, erythrocyte fatty acids, and micronutrients). We performed univariate and multivariate analyses with linear regression models. RESULTS: The mean age at the first KRL assessment was 12.2 ± 3.8 years. Factors that correlated with decreased antioxidant capacity were mostly related to the severity of pulmonary disease [ forced expiratory volume at 1 second (FEV1), acute exacerbation, and congestion. In multivariate analysis, the correlation between Brasfield score and erythrocyte antioxidant potential remained significant (ß = - 0.611, p < 0.001). Among nutritional factors, the ω6/ω3 ratio was significantly correlated to erythrocyte antioxidant potential (ß = - 1.213, p = 0.01). CONCLUSION: The blood antioxidant capability, measured by the KRL test, appears to be an interesting biomarker to evaluate oxidative stress in CF. This study suggests that the ω6/ω3 ratio should be regarded as a nutritional marker in antioxidant management in CF children.


Asunto(s)
Antioxidantes/análisis , Fibrosis Quística/fisiopatología , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Estrés Oxidativo , Adolescente , Antropometría , Biomarcadores/sangre , Niño , Fibrosis Quística/sangre , Eritrocitos/química , Femenino , Humanos , Masculino , Estado Nutricional , Pruebas de Función Respiratoria , Estudios Retrospectivos , Factores Sexuales
10.
JCI Insight ; 7(4)2022 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-35041621

RESUMEN

Impaired glucose metabolism is observed in obesity and type 2 diabetes. Glucose controls gene expression through the transcription factor ChREBP in liver and adipose tissues. Mlxipl encodes 2 isoforms: ChREBPα, the full-length form (translocation into the nucleus is under the control of glucose), and ChREBPß, a constitutively nuclear shorter form. ChREBPß gene expression in white adipose tissue is strongly associated with insulin sensitivity. Here, we investigated the consequences of ChREBPß deficiency on insulin action and energy balance. ChREBPß-deficient male and female C57BL6/J and FVB/N mice were produced using CRISPR/Cas9-mediated gene editing. Unlike global ChREBP deficiency, lack of ChREBPß showed modest effects on gene expression in adipose tissues and the liver, with variations chiefly observed in brown adipose tissue. In mice fed chow and 2 types of high-fat diets, lack of ChREBPß had moderate effects on body composition and insulin sensitivity. At thermoneutrality, ChREBPß deficiency did not prevent the whitening of brown adipose tissue previously reported in total ChREBP-KO mice. These findings revealed that ChREBPß is dispensable for metabolic adaptations to nutritional and thermic challenges.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Glucemia/metabolismo , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/genética , Metabolismo Energético/genética , Regulación de la Expresión Génica , ARN/genética , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/biosíntesis , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL
11.
Metabolites ; 11(5)2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-34064856

RESUMEN

Lipids are essential cellular constituents that have many critical roles in physiological functions. They are notably involved in energy storage and cell signaling as second messengers, and they are major constituents of cell membranes, including lipid rafts. As a consequence, they are implicated in a large number of heterogeneous diseases, such as cancer, diabetes, neurological disorders, and inherited metabolic diseases. Due to the high structural diversity and complexity of lipid species, the presence of isomeric and isobaric lipid species, and their occurrence at a large concentration scale, a complete lipidomic profiling of biological matrices remains challenging, especially in clinical contexts. Using supercritical fluid chromatography coupled with high-resolution mass spectrometry, we have developed and validated an untargeted lipidomic approach to the profiling of plasma and blood. Moreover, we have tested the technique using the Dry Blood Spot (DBS) method and found that it allows for the easy collection of blood for analysis. To develop the method, we performed the optimization of the separation and detection of lipid species on pure standards, reference human plasma (SRM1950), whole blood, and DBS. These analyses allowed an in-house lipid data bank to be built. Using the MS-Dial software, we developed an automatic process for the relative quantification of around 500 lipids species belonging to the 6 main classes of lipids (including phospholipids, sphingolipids, free fatty acids, sterols, and fatty acyl-carnitines). Then, we compared the method using the published data for SRM 1950 and a mouse blood sample, along with another sample of the same blood collected using the DBS method. In this study, we provided a method for blood lipidomic profiling that can be used for the easy sampling of dry blood spots.

12.
Am J Pathol ; 174(3): 1075-83, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19218346

RESUMEN

Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45(+) leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45(+) populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation.


Asunto(s)
Tejido Adiposo/fisiología , Amina Oxidasa (conteniendo Cobre)/deficiencia , Amina Oxidasa (conteniendo Cobre)/genética , Moléculas de Adhesión Celular/deficiencia , Moléculas de Adhesión Celular/genética , Leucocitos/fisiología , Monoaminooxidasa/deficiencia , Semicarbacidas/farmacología , Tejido Adiposo/patología , Animales , Citometría de Flujo , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Obesidad/genética
13.
JCI Insight ; 5(6)2020 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-32106110

RESUMEN

We hypothesized that skeletal muscle contraction produces a cellular stress signal, triggering adipose tissue lipolysis to sustain fuel availability during exercise. The present study aimed at identifying exercise-regulated myokines, also known as exerkines, able to promote lipolysis. Human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation (EPS) to mimic either acute intense or chronic moderate exercise. Conditioned media (CM) experiments with human adipocytes were performed. CM and human plasma samples were analyzed using unbiased proteomic screening and/or ELISA. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples. CM from both acute intense and chronic moderate exercise increased basal lipolysis in human adipocytes. Growth and differentiation factor 15 (GDF15) gene expression and secretion increased rapidly upon skeletal muscle contraction. GDF15 protein was upregulated in CM from both acute and chronic exercise-stimulated myotubes. We further showed that physiological concentrations of recombinant GDF15 protein increased lipolysis in human adipose tissue, while blocking GDF15 with a neutralizing antibody abrogated EPS CM-mediated lipolysis. We herein provide the first evidence to our knowledge that GDF15 is a potentially novel exerkine produced by skeletal muscle contraction and able to target human adipose tissue to promote lipolysis.


Asunto(s)
Ejercicio Físico/fisiología , Factor 15 de Diferenciación de Crecimiento/metabolismo , Lipólisis/fisiología , Músculo Esquelético/metabolismo , Adulto , Humanos , Masculino
14.
Am J Clin Nutr ; 109(6): 1499-1510, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30869115

RESUMEN

BACKGROUND: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders. OBJECTIVES: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss. METHODS: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting. RESULTS: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor α, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion. CONCLUSIONS: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.


Asunto(s)
Adipoquinas/genética , Apolipoproteínas M/genética , Obesidad/dietoterapia , Obesidad/genética , Adipocitos/metabolismo , Adipoquinas/metabolismo , Apolipoproteínas M/metabolismo , Restricción Calórica , Ensayos Clínicos como Asunto , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad/metabolismo
15.
Nat Metab ; 1(1): 133-146, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-32694809

RESUMEN

Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency-mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBPα impairs ChREBPα translocation into the nucleus and induction of ChREBPß, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL-ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity.


Asunto(s)
Adipocitos/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Resistencia a la Insulina , Insulina/metabolismo , Esterol Esterasa/metabolismo , Tejido Adiposo/metabolismo , Animales , Biomarcadores , Elongasas de Ácidos Grasos/genética , Elongasas de Ácidos Grasos/metabolismo , Expresión Génica , Glucosa/metabolismo , Resistencia a la Insulina/genética , Fluidez de la Membrana/genética , Ratones , Ratones Transgénicos , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas , Transducción de Señal
17.
Clin Nutr ESPEN ; 23: 141-147, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29460790

RESUMEN

BACKGROUND & AIMS: Haemorrhagic radiation cystitis (HRC) is a late complication of pelvic radiotherapy. Severe cases are difficult to treat due to persistent or recurrent bleeding, despite urological and hyperbaric oxygen therapy (HBOT). However, wound healing requires a good nutritional status. In this respect, we aimed at analysing the nutritional status of patients with HRC prior to the onset of HBOT and at highlighting predictive nutritional factors of outcome. METHODS: Data were retrospectively collected from a cohort of 179 patients with HRC (between 2011 and 2015). Haematuria was graded according to the Subjective, Objective, Management, Analytic scale (SOMA): grade-4 (n = 46) was compared with grade-3 (n = 56), and with grades 1 and 2 (n = 77). S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium, and essential fatty acids were evaluated before HBOT. HBOT response was measured at 3 months according to the haematuria SOMA grade. The Mann-Whitney test, Fisher's exact test and principal-component analysis were used to compare groups. RESULTS: Patients with higher haematuria grades (3 and 4) harboured significant deficiencies in S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium and essential fatty acids. Moreover, grade-4 patients without improvement after 3 months of HBOT had significant lower initial levels of S-albumin, vitamin C, selenium and linoleic acid. Vitamin C levels <2.5 mg/L were strongly associated with HBOT non-response (OR 23.14, 95% CI 3.73-143.69, p = 0.002). CONCLUSIONS: Our analyses show serious nutritional deficiencies associated with higher grades of HRC and worse prognoses. Patients with haemorrhagic cystitis might benefit from an adequate dietary supplementation to support healing of their bladder mucosa.


Asunto(s)
Cistitis/terapia , Oxigenoterapia Hiperbárica , Desnutrición/epidemiología , Micronutrientes/deficiencia , Deficiencia de Proteína/epidemiología , Traumatismos por Radiación/terapia , Adulto , Anciano , Anciano de 80 o más Años , Cistitis/sangre , Proteínas en la Dieta , Femenino , Estudios de Seguimiento , Humanos , Masculino , Desnutrición/sangre , Desnutrición/diagnóstico , Micronutrientes/sangre , Persona de Mediana Edad , Estado Nutricional , Prevalencia , Análisis de Componente Principal , Deficiencia de Proteína/sangre , Deficiencia de Proteína/diagnóstico , Traumatismos por Radiación/sangre , Estudios Retrospectivos
18.
FEBS Lett ; 580(27): 6391-8, 2006 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-17098232

RESUMEN

Adipose tissues are differently involved in lipid metabolism and obesity according to their type and location. Increasing reports stress on the impact of redox metabolism on obesity and metabolic syndrome. The aim of this work is to investigate the site-specific redox metabolism in three different adipose tissues and its changes occurring in obesity. We analysed enzymatic and non-enzymatic parameters, and focused on the reduced/oxidized glutathione and coenzyme Q couples. In lean compared with obese non-diabetic Zucker rats, interscapular brown fat seems well protected against oxidative stress and epididymal adipose tissue shows a more reduced glutathione redox state, associated with a higher susceptibility to lipophilic oxidative stress than inguinal adipose tissue. Epididymal adipose tissue redox metabolism significantly differs from inguinal one by its limited redox metabolism adaptation. Our results demonstrate site-specific managements of reactive oxygen species metabolism in obese Zucker rats. These results are not consistent with the classic deciphering of inflammatory situation and produce a new conception of the redox parameters implication in the development of the metabolic syndrome.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Glutatión/metabolismo , Obesidad/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Ubiquinona/metabolismo , Tejido Adiposo Pardo/patología , Animales , Epidídimo/metabolismo , Epidídimo/patología , Femenino , Inflamación/metabolismo , Inflamación/patología , Masculino , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Obesidad/patología , Oxidación-Reducción , Ratas , Ratas Zucker
19.
Biochem Pharmacol ; 70(1): 90-101, 2005 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-15894294

RESUMEN

Although it is well accepted that treatment with nucleoside reverse transcriptase inhibitors (NRTIs) modifies fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examines the effects of chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) on the mitochondrial metabolism and the redox status management of rat white adipose tissues originating from two anatomical sites, as well as of the rat liver. Results showed that AZT treatment induced differential effects on the mitochondrial functions depending on the anatomical localisation. Indeed, in inguinal adipose tissue, a significant decrease in the cytochrome c oxidase activity and in the mitochondrial DNA (mtDNA) content was observed, whereas the activity of citrate synthase, a mitochondrial protein exclusively encoded by the nucleus, was not affected. In contrast, no significant change in these parameters could be detected for epididymal tissue and for liver. In parallel, no oxidative stress could be detected after treatment, for both white adipose tissues and for liver, even though treated liver exhibited several modifications in redox management. Taken together, these data demonstrate differential mitochondrial effects of AZT on subcutaneous versus visceral white adipose tissue. Moreover, the decrease in mitochondrial oxidative capacity of inguinal adipocyte consecutive to AZT treatment is not primarily due to an oxidative stress per se, but rather to a depletion of the mtDNA content per cell.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Fármacos Anti-VIH/toxicidad , Síndrome de Lipodistrofia Asociada a VIH/etiología , Mitocondrias/efectos de los fármacos , Zidovudina/toxicidad , Tejido Adiposo/metabolismo , Animales , ADN Mitocondrial/análisis , Complejo IV de Transporte de Electrones/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Mitocondrias/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Ácido Pirúvico/sangre , Ratas , Ratas Wistar , Aumento de Peso/efectos de los fármacos
20.
Biochimie ; 95(11): 2177-81, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23954620

RESUMEN

In septic shock patients, alterations of plasma phospholipid fatty acid profile have never been described. The purpose of this monocentric, non-interventional, observational prospective study was to describe this fatty acid profile in the early phase of septic shock in intensive care unit. Thirty-seven adult patients with septic shock were included after the first day of stay in intensive care unit, before any form of artificial nutritional support. Plasma phospholipid fatty acid composition was determined by gas chromatography. All biological data from patients with septic shock were compared with laboratory reference values. Patients presented hypocholesterolemia and hypertriglyceridemia. They had low concentrations of phospholipid fatty acids specifically n-6 and n-3 polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma phospholipid PUFA concentrations were strongly correlated with cholesterolemia. PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids) ratios were low because of low percentage of n-6 and n-3 PUFAs and high percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (≥20 carbons) were significantly associated with mortality at 28th day. In conclusion, plasma phospholipid FA profile of septic patients is very characteristic, close to that of acute respiratory distress syndrome and mortality is associated with long chain PUFA decrease. This profile could be explained by numerous non-exclusive physio-pathological processes 1) an activation of hepatic de novo lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress, 4) an over-production of inflammatory lipid mediators.


Asunto(s)
Ácidos Grasos Insaturados/sangre , Hipertrigliceridemia/sangre , Fosfolípidos/sangre , Choque Séptico/sangre , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Adulto , Cromatografía de Gases , Femenino , Radicales Libres/toxicidad , Humanos , Hipertrigliceridemia/complicaciones , Hipertrigliceridemia/patología , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Choque Séptico/complicaciones , Choque Séptico/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA