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1.
JAMA Netw Open ; 7(3): e243604, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38526491

RESUMEN

Importance: Sarcopenia and obesity are 2 global concerns associated with adverse health outcomes in older people. Evidence on the population-based prevalence of the combination of sarcopenia with obesity (sarcopenic obesity [SO]) and its association with mortality are still limited. Objective: To investigate the prevalence of sarcopenia and SO and their association with all-cause mortality. Design, Setting, and Participants: This large-scale, population-based cohort study assessed participants from the Rotterdam Study from March 1, 2009, to June 1, 2014. Associations of sarcopenia and SO with all-cause mortality were studied using Kaplan-Meier curves, Cox proportional hazards regression, and accelerated failure time models fitted for sex, age, and body mass index (BMI). Data analysis was performed from January 1 to April 1, 2023. Exposures: The prevalence of sarcopenia and SO, measured based on handgrip strength and body composition (BC) (dual-energy x-ray absorptiometry) as recommended by current consensus criteria, with probable sarcopenia defined as having low handgrip strength and confirmed sarcopenia and SO defined as altered BC (high fat percentage and/or low appendicular skeletal muscle index) in addition to low handgrip strength. Main Outcome and Measure: The primary outcome was all-cause mortality, collected using linked mortality data from general practitioners and the central municipal records, until October 2022. Results: In the total population of 5888 participants (mean [SD] age, 69.5 [9.1] years; mean [SD] BMI, 27.5 [4.3]; 3343 [56.8%] female), 653 (11.1%; 95% CI, 10.3%-11.9%) had probable sarcopenia and 127 (2.2%; 95% CI, 1.8%-2.6%) had confirmed sarcopenia. Sarcopenic obesity with 1 altered component of BC was present in 295 participants (5.0%; 95% CI, 4.4%-5.6%) and with 2 altered components in 44 participants (0.8%; 95% CI, 0.6%-1.0%). An increased risk of all-cause mortality was observed in participants with probable sarcopenia (hazard ratio [HR], 1.29; 95% CI, 1.14-1.47) and confirmed sarcopenia (HR, 1.93; 95% CI, 1.53-2.43). Participants with SO plus 1 altered component of BC (HR, 1.94; 95% CI, 1.60-2.33]) or 2 altered components of BC (HR, 2.84; 95% CI, 1.97-4.11) had a higher risk of mortality than those without SO. Similar results for SO were obtained for participants with a BMI of 27 or greater. Conclusions and Relevance: In this study, sarcopenia and SO were found to be prevalent phenotypes in older people and were associated with all-cause mortality. Additional alterations of BC amplified this risk independently of age, sex, and BMI. The use of low muscle strength as a first step of both diagnoses may allow for early identification of individuals at risk for premature mortality.


Asunto(s)
Sarcopenia , Humanos , Femenino , Anciano , Masculino , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Estudios de Cohortes , Fuerza de la Mano , Fuerza Muscular , Obesidad/complicaciones , Obesidad/epidemiología
2.
Sci Rep ; 14(1): 3108, 2024 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326394

RESUMEN

TRUEFAD (TRUE Fiber Atrophy Distinction) is a bioimagery user-friendly tool developed to allow consistent and automatic measurement of myotube diameter in vitro, muscle fiber size and type using rodents and human muscle biopsies. This TRUEFAD package was set up to standardize and dynamize muscle research via easy-to-obtain images run on an open-source plugin for FIJI. We showed here both the robustness and the performance of our pipelines to correctly segment muscle cells and fibers. We evaluated our pipeline on real experiment image sets and showed consistent reliability across images and conditions. TRUEFAD development makes possible systematical and rapid screening of substances impacting muscle morphology for helping scientists focus on their hypothesis rather than image analysis.


Asunto(s)
Fibras Musculares Esqueléticas , Programas Informáticos , Humanos , Reproducibilidad de los Resultados , Fibras Musculares Esqueléticas/fisiología , Procesamiento de Imagen Asistido por Computador/métodos , Técnicas de Cultivo de Célula
3.
J Physiol Biochem ; 80(2): 287-302, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38175500

RESUMEN

Previous studies in Western diet (WD)-fed male rats have highlighted a link between the stimulation of cardiac contractility, mitochondrial adaptations and a pro-inflammatory fatty acid profile of phospholipids in the heart. Our objectives were to determine (1) if WD-fed female Wistar rats and obese humans display a similar pro-inflammatory profile in their cardiac phospholipids and (2) if this lipid profile is associated with deleterious effects on the heart of the female rodents. Female Wistar rats were fed WD for 5 weeks or a laboratory chow as a control. Ionic homeostasis, redox status, inflammation markers, and fatty acid composition of phospholipids were analysed in the heart. WD increased the abdominal fat mass without modifying the body weight of female rats. As previously found in males, a WD induced a shift in membrane fatty acid composition toward a pro-inflammatory profile in the female rats, but not in obese humans. It was associated with an increased COX2 expression suggesting an increased pro-inflammatory eicosanoid production. Signs of increased intracellular calcium strongly supported a stimulation of cardiac contractility without any induction of apoptosis. The heart of WD-fed rats exhibited a hypoxic state as a higher HIF1-α expression was reported. The expressions of antioxidant enzymes were increased, but the redox reserves against reactive oxygen species were lowered. In conclusion, as previously observed in males, we suppose that cardiac abnormalities are magnified with severe obesity in female rats, leading to hypoxia and intense oxidative stress which could ultimately induce cell death and heart failure.


Asunto(s)
Dieta Occidental , Hipoxia , Contracción Miocárdica , Ratas Wistar , Animales , Femenino , Dieta Occidental/efectos adversos , Hipoxia/metabolismo , Hipoxia/fisiopatología , Miocardio/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratas , Ciclooxigenasa 2/metabolismo , Estrés Oxidativo , Fosfolípidos/metabolismo , Obesidad/metabolismo , Obesidad/etiología , Obesidad/fisiopatología , Modelos Animales de Enfermedad , Masculino , Humanos
4.
Life Sci ; 327: 121826, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37270172

RESUMEN

AIMS: Rheumatoid arthritis is an autoimmune disease which induces chronic inflammation and increases the risk for sarcopenia and metabolic abnormalities. Nutritional strategies using omega 3 polyunsaturated fatty acids could be proposed to alleviate inflammation and improve the maintenance of lean mass. Independently, pharmacological agents targeting key molecular regulators of the pathology such as TNF alpha could be proposed, but multiple therapies are frequently necessary increasing the risk for toxicity and adverse effects. The aim of the present study was to explore if the combination of an anti-TNF therapy (Etanercept) with dietary supplementation with omega 3 PUFA could prevent pain and metabolic effects of RA. MATERIALS AND METHODS: RA was induced using collagen-induced arthritis (CIA) in rats to explore of supplementation with docosahexaenoic acid, treatment with etanercept or their association could alleviate symptoms of RA (pain, dysmobility), sarcopenia and metabolic alterations. KEY FINDINGS: We observed that Etanercept had major benefits on pain and RA scoring index. However, DHA could reduce the impact on body composition and metabolic alterations. SIGNIFICANCE: This study revealed for the first time that nutritional supplementation with omega 3 fatty acid could reduce some symptoms of rheumatoid arthritis and be an effective preventive treatment in patients who do not need pharmacological therapy, but no sign of synergy with an anti-TNF agent was observed.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Ácidos Grasos Omega-3 , Sarcopenia , Ratas , Animales , Etanercept/farmacología , Etanercept/uso terapéutico , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Inhibidores del Factor de Necrosis Tumoral , Artritis Reumatoide/tratamiento farmacológico , Ácidos Grasos Omega-3/uso terapéutico , Inflamación , Dolor/tratamiento farmacológico
5.
J. physiol. biochem ; 79(2): 441-450, may. 2023.
Artículo en Inglés | IBECS | ID: ibc-222554

RESUMEN

Alterations in adipose tissue (AT) metabolism related to inflammation and adipokine’s production lead to perturbations in its capacity to store lipids and release fatty acids (FA) during feeding/fasting transition or during exercise. Exercise has a beneficial effect on AT metabolism, but conventional trainings are not always suitable for patients with functional limitations. Dynamic eccentric (ECC) exercise prevents the accumulation of AT and may then overcome those limitations. Consequently, this study aimed at investigating AT’s adaptations after ECC training. Nine-week-old male rats were randomly assigned to a control sedentary or three-trained groups for which treadmill slopes modulated exercise oxygen consumption (VO2) and mechanical work (n = 15 per group): (1) + 15% uphill-concentric group (CONC), (2) − 15% downhill group (ECC15, same mechanical work as CONC) and (3) − 30% downhill group (ECC30, same VO2, or oxygen cost as CONC). Body composition and energy expenditure (EE) were measured before and after 8 weeks of training. Subcutaneous AT was collected to study total FA profile and gene expression. Higher total EE was driven by lean mass gain in trained animals. In AT, there was a decrease in arachidonic acid with CONC or ECC15 training. Increased adiponectin, leptin, lipases, Glut4 and Igf1 mRNA levels in ECC15 group suggested major metabolic adaption in AT. In conclusion, ECC could induce beneficial modifications in AT fatty acid profile and the expression of key genes related to metabolism and insulin sensitivity. (AU)


Asunto(s)
Animales , Ratas , Tejido Adiposo/metabolismo , Condicionamiento Físico Animal , Biología , Metabolismo Energético , Músculo Esquelético/metabolismo , Consumo de Oxígeno
6.
Curr Opin Clin Nutr Metab Care ; 26(2): 189-194, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36892966

RESUMEN

PURPOSE OF REVIEW: An increase in the plant-based characteristics of the diet is now recommended for human and planetary health. There is growing evidence that plant protein (PP) intake has beneficial effects on cardiometabolic risk. However, proteins are not consumed isolated and the protein package (lipid species, fiber, vitamins, phytochemicals, etc) may contribute, besides the protein effects per se, to explain the beneficial effects associated with PP-rich diets. RECENT FINDINGS: Recent studies have shown the potential of nutrimetabolomics to apprehend the complexity of both the human metabolism and the dietary habits, by providing signatures associated to the consumption of PP-rich diets. Those signatures comprised an important proportion of metabolites that were representative of the protein package, including specific amino acids (branched-chain amino acids and their derivates, glycine, lysine), but also lipid species (lysophosphatidylcholine, phosphatidylcholine, plasmalogens) and polyphenol metabolites (catechin sulfate, conjugated valerolactones and phenolic acids). SUMMARY: Further studies are needed to go deeper in the identification of all metabolites making part of the specific metabolomic signatures, associated to the large range of protein package constituents and their effects on the endogenous metabolism, rather than to the protein fraction itself. The objective is to determine the bioactive metabolites, as well as the modulated metabolic pathways and the mechanisms responsible for the observed effects on cardiometabolic health.


Asunto(s)
Aminoácidos , Enfermedades Cardiovasculares , Humanos , Proteínas de Plantas , Metabolómica , Enfermedades Cardiovasculares/prevención & control , Lípidos
7.
J Physiol Biochem ; 79(2): 441-450, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36961725

RESUMEN

Alterations in adipose tissue (AT) metabolism related to inflammation and adipokine's production lead to perturbations in its capacity to store lipids and release fatty acids (FA) during feeding/fasting transition or during exercise. Exercise has a beneficial effect on AT metabolism, but conventional trainings are not always suitable for patients with functional limitations. Dynamic eccentric (ECC) exercise prevents the accumulation of AT and may then overcome those limitations. Consequently, this study aimed at investigating AT's adaptations after ECC training. Nine-week-old male rats were randomly assigned to a control sedentary or three-trained groups for which treadmill slopes modulated exercise oxygen consumption (VO2) and mechanical work (n = 15 per group): (1) + 15% uphill-concentric group (CONC), (2) - 15% downhill group (ECC15, same mechanical work as CONC) and (3) - 30% downhill group (ECC30, same VO2, or oxygen cost as CONC). Body composition and energy expenditure (EE) were measured before and after 8 weeks of training. Subcutaneous AT was collected to study total FA profile and gene expression. Higher total EE was driven by lean mass gain in trained animals. In AT, there was a decrease in arachidonic acid with CONC or ECC15 training. Increased adiponectin, leptin, lipases, Glut4 and Igf1 mRNA levels in ECC15 group suggested major metabolic adaption in AT. In conclusion, ECC could induce beneficial modifications in AT fatty acid profile and the expression of key genes related to metabolism and insulin sensitivity.


Asunto(s)
Tejido Adiposo , Condicionamiento Físico Animal , Masculino , Ratas , Animales , Tejido Adiposo/metabolismo , Consumo de Oxígeno , Metabolismo Energético , Biología , Músculo Esquelético/metabolismo
8.
Crit Rev Food Sci Nutr ; 63(32): 11185-11210, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35730212

RESUMEN

Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades Metabólicas , Microbiota , Humanos , Anciano , Envejecimiento/fisiología , Enfermedades Metabólicas/prevención & control , Microbioma Gastrointestinal/fisiología , Valor Nutritivo
9.
Int J Mol Sci ; 23(11)2022 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-35682570

RESUMEN

The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn's disease (CD). The aim of this study was to assess the effects of rebalancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Paraprevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect.


Asunto(s)
Enfermedad de Crohn , Lino , Microbiota , Animales , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/microbiología , Dieta Alta en Grasa , Suplementos Dietéticos , Modelos Animales de Enfermedad , Escherichia coli , Mucosa Intestinal/microbiología , Aceite de Linaza/farmacología , Ratones , Ratones Transgénicos
10.
Metabolites ; 11(12)2021 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-34940596

RESUMEN

Obesity is characterized by profound alterations in adipose tissue (AT) biology, leading to whole body metabolic disturbances such as insulin resistance and cardiovascular diseases. These alterations are related to the development of a local inflammation, fibrosis, hypertrophy of adipocytes, and dysregulation in energy homeostasis, notably in visceral adipose tissue (VAT). Omega 3 (n-3) fatty acids (FA) have been described to possess beneficial effects against obesity-related disorders, including in the AT; however, the long-term effect across generations remains unknown. The current study was conducted to identify if supplementation with n-3 polyunsaturated FA (PUFA) for three generations could protect from the consequences of an obesogenic diet in VAT. Young mice from the third generation of a lineage receiving a daily supplementation (1% of the diet) with fish oil rich in eicosapentaenoic acid (EPA) or an isocaloric amount of sunflower oil, were fed a high-fat, high-sugar content diet for 4 months. We explore the transcriptomic adaptations in each lineage using DNA microarray in VAT and bioinformatic exploration of biological regulations using online databases. Transgenerational intake of EPA led to a reduced activation of inflammatory processes, perturbation in metabolic homeostasis, cholesterol metabolism, and mitochondrial functions in response to the obesogenic diet as compared to control mice from a control lineage. This suggests that the continuous intake of long chain n-3 PUFA could be preventive in situations of oversupply of energy-dense, nutrient-poor foods.

11.
Nutrients ; 13(12)2021 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-34959754

RESUMEN

This study evaluates the capacity of a bread enriched with fermentable dietary fibres to modulate the metabolism and nutrients handling between tissues, gut and peripheral, in a context of overfeeding. Net fluxes of glucose, lactate, urea, short chain fatty acids (SCFA), and amino acids were recorded in control and overfed female mini-pigs supplemented or not with fibre-enriched bread. SCFA in fecal water and gene expressions, but not protein levels or metabolic fluxes, were measured in muscle, adipose tissue, and intestine. Fibre supplementation increased the potential for fatty acid oxidation and mitochondrial activity in muscle (acox, ucp2, sdha and cpt1-m, p < 0.05) as well as main regulatory transcription factors of metabolic activity such as pparα, pgc-1α and nrf2. All these features were associated with a reduced muscle fibre cross sectional area, resembling to controls (i.e., lean phenotype). SCFA may be direct inducers of these cross-talk alterations, as their feces content (+52%, p = 0.05) was increased in fibre-supplemented mini-pigs. The SCFA effects could be mediated at the gut level by an increased production of incretins (increased gcg mRNA, p < 0.05) and an up-regulation of SCFA receptors (increased gpr41 mRNA, p < 0.01). Hence, consumption of supplemented bread with fermentable fibres can be an appropriate strategy to activate muscle energy catabolism and limit the establishment of an obese phenotype.


Asunto(s)
Tejido Adiposo/metabolismo , Fibras de la Dieta/administración & dosificación , Metabolismo Energético/efectos de los fármacos , Músculo Esquelético/metabolismo , Hipernutrición/metabolismo , Aminoácidos/metabolismo , Animales , Pan , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ácidos Grasos Volátiles/metabolismo , Heces/química , Femenino , Alimentos Fermentados , Glucosa/metabolismo , Incretinas/metabolismo , Intestinos/metabolismo , Ácido Láctico/metabolismo , Porcinos , Porcinos Enanos , Urea/metabolismo
12.
Nutrients ; 13(10)2021 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-34684532

RESUMEN

High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.


Asunto(s)
Suplementos Dietéticos , Conducta Alimentaria , Entrenamiento de Intervalos de Alta Intensidad , Aceite de Linaza/farmacología , Obesidad/patología , Estrés Oxidativo , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Catalasa/metabolismo , Conducta Alimentaria/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Nitratos/metabolismo , Obesidad/sangre , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Tejido Subcutáneo/efectos de los fármacos , Tejido Subcutáneo/metabolismo , Superóxido Dismutasa/metabolismo , Regulación hacia Arriba/efectos de los fármacos
13.
Nutrients ; 13(3)2021 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-33673609

RESUMEN

Obesity, a major public health problem, is the consequence of an excess of body fat and biological alterations in the adipose tissue. Our aim was to determine whether high-intensity interval training (HIIT) and/or α-linolenic acid supplementation (to equilibrate the n-6/n-3 polyunsaturated fatty acids (PUFA) ratio) might prevent obesity disorders, particularly by modulating the mucosa-associated microbiota. Wistar rats received a low fat diet (LFD; control) or high fat diet (HFD) for 16 weeks to induce obesity. Then, animals in the HFD group were divided in four groups: HFD (control), HFD + linseed oil (LO), HFD + HIIT, HFD + HIIT + LO. In the HIIT groups, rats ran on a treadmill, 4 days.week-1. Erythrocyte n-3 PUFA content, body composition, inflammation, and intestinal mucosa-associated microbiota composition were assessed after 12 weeks. LO supplementation enhanced α-linolenic acid (ALA) to docosahexaenoic acid (DHA) conversion in erythrocytes, and HIIT potentiated this conversion. Compared with HFD, HIIT limited weight gain, fat mass accumulation, and adipocyte size, whereas LO reduced systemic inflammation. HIIT had the main effect on gut microbiota ß-diversity, but the HIIT + LO association significantly increased Oscillospira relative abundance. In our conditions, HIIT had a major effect on body fat mass, whereas HIIT + LO improved ALA conversion to DHA and increased the abundance of Oscillospira bacteria in the microbiota.


Asunto(s)
Clostridiales/efectos de los fármacos , Ácidos Docosahexaenoicos/metabolismo , Condicionamiento Físico Animal , Ácido alfa-Linolénico/farmacología , Adipocitos , Animales , Glucemia , Composición Corporal , Eritrocitos , Ácidos Grasos , Ácidos Grasos Volátiles/química , Heces/química , Microbioma Gastrointestinal , Prueba de Tolerancia a la Glucosa , Entrenamiento de Intervalos de Alta Intensidad , Mucosa Intestinal , Distribución Aleatoria , Ratas , Ratas Wistar , Ácido alfa-Linolénico/administración & dosificación
14.
Eur J Nutr ; 60(6): 3143-3157, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33543364

RESUMEN

PURPOSE: The effect of manipulating the fatty acid profile of the diet over generations could affect the susceptibility to develop obesity and metabolic disorders. Although some acute effects were described, the impact of transgenerational continuous supplementation with omega 3 fatty acids on metabolic homeostasis and skeletal muscle metabolic flexibility during a nutritional stress is unknown. METHODS: We analyzed the effect of an obesogenic diet in mice after transgenerational supplementation with an omega-3 rich oil (mainly EPA) or a control oil. Young F3 animals received a high fat and high sucrose diet for 4 months. Whole-body biometric data were recorded and lipidomic/transcriptomic adaptations were explored in the skeletal muscle. RESULTS: F3 mice from the lineage supplemented with EPA gained less weight, fat mass, and exhibited better metabolic parameters after the obesogenic diet compared to mice from the control lineage. Transcriptomic exploration of skeletal muscle showed differential regulation of biological processes such as fibrosis, fatty acid catabolism, and inflammation between lineages. These adaptations were associated to subtle lipid remodeling of cellular membranes with an enrichment in phospholipids with omega 3 fatty acid in mice from the EPA lineage. CONCLUSION: Transgenerational and continuous intake of EPA could help to reduce cardiovascular and metabolic risks related to an unbalanced diet by the modulation of insulin sensitivity, fatty acid metabolism, and fibrosis in skeletal muscle.


Asunto(s)
Ácido Eicosapentaenoico , Ácidos Grasos Omega-3 , Animales , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético
15.
Front Physiol ; 12: 749049, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35111075

RESUMEN

The phenotype of sarcopenic obesity is frequently associated with impaired muscle strength and performance. Ectopic lipid deposition may interfere with muscle anabolic response especially during aging. Evidence is scarce concerning the potential interplay among aging and nutrient imbalance on skeletal muscle functionality. The objective of the present study was to investigate the impact of protein intake in the context of an obesogenic diet on skeletal muscle functional properties and intramuscular lipid infiltration. Two groups of forty-two adult and thirty-seven old male Wistar rats were randomly divided into four groups: isocaloric standard diet (12% protein, 14% lipid, as ST12); isocaloric standard (high-protein) diet (25% protein, 14% lipid, ST25); hypercaloric high-fat (normal-protein) diet (12% protein, 45% lipid, HF12); and hypercaloric high-fat (high-protein) diet (25% protein, 45% lipid, HF25). The nutritional intervention lasted 10 weeks. Total body composition was measured through Echo-MRI. Lipids were extracted from tibialis anterior muscle and analyzed by gas-liquid chromatography. The functional properties of the plantarflexor muscles were evaluated in vivo on an isokinetic dynamometer. Maximal torque was assessed from the torque-frequency relationship in isometric condition and maximal power was evaluated from the torque-velocity relationship in concentric condition. In adult rats high-protein intake combined with high-fat diet determined a lower decrease in relative isometric torque, normalized to either FFM or body weight, compared with adult rats fed a high-fat normal-protein diet. High-fat diet was also detrimental to relative muscle power, as normalized to body weight, that decreased to a larger extent in adult rats fed a high-fat normal-protein diet than their counterparts fed a normal-fat, high-protein diet. The effect of high-fat diet observed in adults, with the enhanced protein intake (25%) conferring some kind of protection against the negative effects of HFD, may be linked to the reduced intramuscular fat in this group, which may have contributed to preserve, at least partly, the contractile properties. A potential role for high-protein diet in preventing ectopic lipid deposition needs to be explored in future research. Detrimental effects of high- fat diet on skeletal muscle performance are mitigated by high- protein intake in adult rats but not in old rats.

16.
Nutrients ; 12(12)2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33348802

RESUMEN

Insulin resistance decreases the ability of insulin to inhibit hepatic gluconeogenesis, a key step in the development of metabolic syndrome. Metabolic alterations, fat accumulation, and fibrosis in the liver are closely related and contribute to the progression of comorbidities, such as hypertension, type 2 diabetes, or cancer. Omega 3 (n-3) polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), were identified as potent positive regulators of insulin sensitivity in vitro and in animal models. In the current study, we explored the effects of a transgenerational supplementation with EPA in mice exposed to an obesogenic diet on the regulation of microRNAs (miRNAs) and gene expression in the liver using high-throughput techniques. We implemented a comprehensive molecular systems biology approach, combining statistical tools, such as MicroRNA Master Regulator Analysis pipeline and Boolean modeling to integrate these biochemical processes. We demonstrated that EPA mediated molecular adaptations, leading to the inhibition of miR-34a-5p, a negative regulator of Irs2 as a master regulatory event leading to the inhibition of gluconeogenesis by insulin during the fasting-feeding transition. Omics data integration provided greater biological insight and a better understanding of the relationships between biological variables. Such an approach may be useful for deriving innovative data-driven hypotheses and for the discovery of molecular-biochemical mechanistic links.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/sangre , Expresión Génica/efectos de los fármacos , Síndrome Metabólico/sangre , MicroARNs/sangre , MicroARNs/efectos de los fármacos , Animales , Dieta Alta en Grasa/métodos , Suplementos Dietéticos , Modelos Animales de Enfermedad , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL
17.
Nutrients ; 12(10)2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33050316

RESUMEN

Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65-79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.


Asunto(s)
Grasas Insaturadas en la Dieta/administración & dosificación , Ingestión de Alimentos/fisiología , Ácidos Grasos Insaturados/administración & dosificación , Ácidos Grasos/efectos adversos , Fenómenos Fisiológicos de la Nutrición/fisiología , Sarcopenia/prevención & control , Anciano , Estudios de Cohortes , Proteínas en la Dieta/administración & dosificación , Ejercicio Físico , Femenino , Fuerza de la Mano , Humanos , Masculino , Ingesta Diaria Recomendada , Riesgo , Sarcopenia/diagnóstico , Sarcopenia/etiología , Factores Sexuales
18.
Antioxidants (Basel) ; 9(5)2020 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-32365668

RESUMEN

It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.

19.
Nutrients ; 12(1)2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31952247

RESUMEN

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by a high prevalence of death due to cardiometabolic diseases. As observed during the aging process, several comorbidities, such as cardiovascular disorders (CVD), insulin resistance, metabolic syndrome and sarcopenia, are frequently associated to RA. These abnormalities could be closely linked to alterations in lipid metabolism. Indeed, RA patients exhibit a lipid paradox, defined by reduced levels of total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol whereas the CVD risk is increased. Moreover, the accumulation of toxic lipid mediators (i.e., lipotoxicity) in skeletal muscles can induce mitochondrial dysfunctions and insulin resistance, which are both crucial determinants of CVD and sarcopenia. The prevention or reversion of these biological perturbations in RA patients could contribute to the maintenance of muscle health and thus be protective against the increased risk for cardiometabolic diseases, dysmobility and mortality. Yet, several studies have shown that omega 3 fatty acids (FA) could prevent the development of RA, improve muscle metabolism and limit muscle atrophy in obese and insulin-resistant subjects. Thereby, dietary supplementation with omega 3 FA should be a promising strategy to counteract muscle lipotoxicity and for the prevention of comorbidities in RA patients.


Asunto(s)
Artritis Reumatoide/complicaciones , Ácidos Grasos Omega-3/farmacología , Sarcopenia/etiología , Sarcopenia/prevención & control , Humanos
20.
Clin Nutr ; 39(5): 1497-1509, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31279616

RESUMEN

BACKGROUND & AIMS: Metabolic syndrome (MetS) induces major disturbances in plasma metabolome, reflecting abnormalities of several metabolic pathways. Recent evidences have demonstrated that the consumption of dairy products may protect from MetS, but the mechanisms remains unknown. The present study aimed at identify how the consumption of different types of dairy products could modify the changes in plasma metabolome during MetS. METHODS: In this observational study, we analyzed how the consumption of dairy products could modify the perturbations in the plasma metabolome induced by MetS in a sample of 298 participants (61 with MetS) from the French MONA LISA survey. Metabolomic profiling was analyzed with UPLC-MS/MS. RESULTS: Subjects with MetS exhibited major changes in plasma metabolome. Significant differences in plasma levels of branched chain amino acids, gamma-glutamyl amino acids, and metabolites from arginine and proline metabolism were observed between healthy control and Mets subjects. Plasma levels of many lipid species were increased with MetS (mono- and diacylglycerols, eicosanoids, lysophospholipids and lysoplasmalogens), with corresponding decreases in short chain fatty acids and plasmalogens. The consumption of dairy products, notably with a low fat content (milk and fresh dairy products), altered metabolite profiles in plasma from MetS subjects. Specifically, increasing consumption of dairy products promoted accumulation of plasma C15:0 fatty acid and was inversely associated to some circulating lysophospholipids, sphingolipids, gamma-glutamyl amino acids, leukotriene B4 and lysoplasmalogens. CONCLUSIONS: the consumption of low fat dairy products could mitigate some of the variations induced by MetS.


Asunto(s)
Productos Lácteos/efectos adversos , Dieta/efectos adversos , Síndrome Metabólico/inducido químicamente , Metabolómica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
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