RESUMEN
PURPOSE: Physical activity (PA) represents the first line of defence against diseases characterised by increased inflammation status, such as metabolic and infectious diseases. Conversely, a sedentary lifestyle-associated with obesity, type 2 diabetes and cardiovascular disorders-negatively impacts on general health status, including susceptibility to infections. At a time of a pandemic SARS-CoV2 infection, and in the context of the multiorgan crosstalk (widely accepted as a mechanism participating in the pathophysiology of all organs and systems), we examine the complex interplay mediated by skeletal muscle contraction involving the immune system and how this contributes to control health status and to counteract viral infections. In so doing, we review the molecular mechanisms and expression of molecules modulated by PA, able to provide the proper molecular equipment against viral infections such as the current SARS-CoV2. METHODS: A critical review of the literature was performed to elucidate the molecular mechanisms and mediators induced by PA that potentially impact on viral infections such as SARS-CoV2. RESULTS: We showed the effects mediated by regular moderate PA on viral adverse effects through the regulation of biological processes involving the crosstalk between skeletal muscle, the immune system and adipose tissue. Evidence was provided of the effects mediated by modulation of the expression of inflammation markers. CONCLUSION: A tigth association between PA and reduction in inflammation status allows effective counteracting of SARS-CoV2 infection. It is therefore essential to persuade people to keep active.
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Betacoronavirus , Infecciones por Coronavirus , Ejercicio Físico , Pandemias , Neumonía Viral , COVID-19 , Infecciones por Coronavirus/inmunología , Humanos , Neumonía Viral/inmunología , SARS-CoV-2RESUMEN
The insulin-like growth factor (IGF) system, which is constituted by the IGF-1 and IGF-2 peptide hormones, their corresponding receptors and several IGF binding proteins, is involved in physiological and pathophysiological processes. The IGF system promotes cancer proliferation/survival and its signaling induces the epithelial-mesenchymal transition (EMT) phenotype, which contributes to the migration, invasiveness, and metastasis of epithelial tumors. These cancers share two major IGF-1R signaling transduction pathways, PI3K/AKT and RAS/MEK/ERK. However, as far as we could review at this time, each type of cancer cell undergoes EMT through tumor-specific routes. Here, we review the tumor-specific molecular signatures of IGF-1-mediated EMT in breast, lung, and gastric cancers.
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Neoplasias de la Mama/patología , Transición Epitelial-Mesenquimal , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Gástricas/patología , Animales , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Neoplasias Pulmonares/metabolismo , Receptor IGF Tipo 1/análisis , Receptor IGF Tipo 1/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismoRESUMEN
A functional relationship is suggested between two well-known protein hormones, insulin-like growth factor 1 (IGF-1) and adiponectin. In the last two decades in fact, different experimental evidence has indicated a non-random link between them. Here, we describe briefly the IGF-1 and adiponectin systems, and we then focus on their putative interplay in relation to several pathological conditions, including obesity, diabetes, insulin resistance, cardiovascular disease, and cancer. Although the existing studies are hardly comparable, they definitely indicate a functional connection between these two protein hormones. In conclusion, the current knowledge strongly encourages further research into the common, as well as novel, mechanisms through which IGF-1 and adiponectin exert their concerted action.
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Adiponectina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adiponectina/genética , Animales , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Diabetes Mellitus/etiología , Diabetes Mellitus/metabolismo , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Humanos , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/genética , Neoplasias/etiología , Neoplasias/metabolismo , Obesidad/etiología , Obesidad/metabolismo , Unión Proteica , Transducción de SeñalRESUMEN
The position of the fatty acids (sn-1, sn-2 and sn-3) (stereospecific numbering (sn)) in triacylglycerol (TAG) molecules produces a characteristic stereospecificity that defines the physical properties of the fats and influences their absorption, metabolism and uptake into tissues. Fat interesterification is a process that implies a positional distribution of fatty acids (FAs) within the TAG molecules, generating new TAG species, without affecting the FA cis-trans natural balance. The interesterified (IE) fats, frequently used in the food industry comprise fats that are rich in long-chain saturated FAs, such as palmitic acid (16:0) and stearic acid (18:0). Within the interesterified fats, a critical role is played by FA occupying the sn-2 position; in fact, the presence of an unsaturated FA in this specific position influences early metabolic processing and postprandial clearance that in turn could induce atherogenesis and thrombogenesis events. Here, we provide an overview on the role of TAG structures and interesterified palmitic and stearic acid-rich fats on fasting and postprandial lipemia, focusing our attention on their physical properties and their effects on human health.
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Grasas de la Dieta/uso terapéutico , Ácidos Grasos/química , Hiperlipidemias/dietoterapia , Aceites de Plantas/química , Ácidos Grasos/uso terapéutico , Humanos , Hiperlipidemias/metabolismo , Ácido Palmítico/química , Ácido Palmítico/uso terapéutico , Aceites de Plantas/uso terapéutico , Ácidos Esteáricos/química , Ácidos Esteáricos/uso terapéutico , Estereoisomerismo , Triglicéridos/química , Triglicéridos/uso terapéuticoRESUMEN
Gene variants in MC4R, SIRT1 and FTO are associated with severe obesity and metabolic impairment in Caucasians. We investigated whether common variants in these genes are associated with metabolic syndrome (MetS) in a large group of morbidly obese young adults from southern Italy. One thousand morbidly obese subjects (62% women, mean body mass index 46.5 kg/m(2), mean age 32.6 years) whose families had lived in southern Italy for at least 2 generations were recruited. Single-nucleotide polymorphisms (SNPs) rs12970134, rs477181, rs502933 (MC4R locus), rs3818292, rs7069102, rs730821, rs2273773, rs12413112 (SIRT1 locus) and rs1421085, rs9939609, 9930506, 1121980 (FTO locus) were genotyped by Taqman assay; blood parameters were assayed by routine methods; the Fat Mass, Fat Free Mass, Respiratory Quotient, Basal Metabolic Rate (BMR) and waist circumference were also determined. Binomial logistic regression showed that the TA heterozygous genotype of SNP rs9939609 in the FTO gene was associated with the presence of MetS in our population [OR (95% CI): 2.53 (1.16-5.55)]. Furthermore, the FTO rs9939609 genotype accounted for 21.3% of the MetS phenotype together with total cholesterol, BMR and age. Our results extend the knowledge on genotype susceptibility for MetS in relation to a specific geographical area of residence.
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Síndrome Metabólico/complicaciones , Síndrome Metabólico/genética , Obesidad Mórbida/genética , Proteínas/genética , Adulto , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Femenino , Estudios de Asociación Genética , Variación Genética , Humanos , Italia , Modelos Logísticos , Masculino , Síndrome Metabólico/patología , Obesidad Mórbida/patología , Polimorfismo de Nucleótido Simple , Receptor de Melanocortina Tipo 4/genética , Sirtuina 1/genéticaAsunto(s)
Trastornos de los Cromosomas/genética , Duplicación Cromosómica/genética , Obesidad/genética , Adulto , Niño , Hibridación Genómica Comparativa , Diabetes Mellitus Tipo 2/genética , Femenino , Humanos , Hipertensión/genética , Italia , Masculino , Persona de Mediana Edad , Fenotipo , Adulto JovenRESUMEN
Health promotion requires good nutrition and an adequate lifestyle, which together contribute to people's well-being [...].
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Deportes , Humanos , Suplementos Dietéticos , Ejercicio Físico , Estado NutricionalRESUMEN
There are a lot of evidences on the beneficial effects mediated by exercise on the prevention of not communicable diseases (NCDs) including different type of cancer. The production of circulating exerkines transported in exosomes represents a novel pathway activated by exercise. However, the biological mechanisms that could explain the role of exosomes in cancer prevention have been not fully elucidated. The aim of this mini-review is to provide an update on the biological mechanisms bringing the release of muscle-derived exosomes during exercise and cancer prevention.
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Background: Physical fitness (PF) levels correlate with health hallmarks at all ages. In this study, w aimed to determine the PF level of schoolchildren from the Campania Region (Italy) through health-related PF (HRPF) components, taking into account body weight and sport practice (SP). Methods: PF level was determined in 565 schoolchildren aged 10−13 (11.7 ± 1.0 yrs; m: 353, f: 212) using some of the Eurofit battery tests. Results: 77% children practiced sport, boys more than girls (86% vs. 63%, respectively; p < 0.05). Boys performed better than girls (p < 0.05) in the Plate Tapping, Standing Broad Jump, Bent-Arm Hang, and 10 × 5 m Shuttle Run tests; girls performed better in the Sit-and-Reach Test (p < 0.05). Conclusion: Overweight/obese status negatively affects the muscular strength of lower limbs, even if it progressively improves during growth. SP was revealed to be a determinant in performance only in some PF tests, likely due to the heterogeneous training level among boys and girls who practice sport.
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Aptitud Física , Deportes , Índice de Masa Corporal , Peso Corporal , Niño , Prueba de Esfuerzo , Femenino , Humanos , Masculino , SobrepesoRESUMEN
The isoforms of lycopene, carotenoids, and their derivatives including precursors of vitamin A are compounds relevant for preventing chronic degenerative diseases such as cardiovascular diseases and cancer. Tomatoes are a major source of these compounds. However, cooking and successive metabolic processes determine the bioavailability of tomatoes in human nutrition. To evaluate the effect of acute/chronic cooking procedures on the bioavailability of lycopene and carotene isoforms in human plasma, we measured the blood levels of these compounds and of the serum antioxidant potential in volunteers after a meal containing two different types of tomato sauce (rustic or strained). Using a randomized cross-over administration design, healthy volunteers were studied, and the above indicated compounds were determined by HPLC. The results indicate an increased bioavailability of the estimated compounds and of the serum antioxidant potential with both types of tomato purée and the subsequently derived sauces (the increase was greater with strained purée). This study sheds light on the content of nutrient precursors of vitamin A and other antioxidant compounds derived from tomatoes cooked with different strategies. Lastly, our study indicates that strained purée should be preferred over rustic purée.
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Antioxidantes/farmacocinética , Culinaria/métodos , Licopeno/sangre , Solanum lycopersicum/química , beta Caroteno/sangre , Adulto , Disponibilidad Biológica , Estudios Cruzados , Femenino , Manipulación de Alimentos/métodos , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Isoformas de Proteínas/farmacocinéticaRESUMEN
Anabolic androgenic steroids, a class of steroid hormones related to testosterone, are natural ligands of androgen receptor (AR), a member of the nuclear receptor superfamily of ligand-activated transcription factors. AR binds specific DNA elements, known as androgen-response elements. Testosterone, the main male sexual hormone, binds AR directly and indirectly, through conversion into dihydrotestosterone (DHT), its more active metabolite. Anabolic androgenic steroids are frequently detected in the urine of doped athletes; their consumption is also growing among sport amateurs and adolescents. The effects of androgens can differ depending on the target cells and/or tissues. To gain insight into transcription activation mechanisms of AR, we investigated AR protein signaling in human peripheral blood lymphocytes treated with supraphysiological doses of DHT. We performed a comparative proteomic analysis and we identified about 30 differentially expressed proteins. At least five species contained a consensus androgen-response elements sequence in the promoter region of related coding genes. The analysis also revealed that high doses of DHT activate the drug detoxification process, could stimulate an increase in cell motility and exert a prosurvival effect rather than an apoptotic one.
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Dihidrotestosterona/farmacología , Leucocitos Mononucleares/metabolismo , Proteoma/efectos de los fármacos , Proteómica/métodos , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacos , Adulto , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Biología Computacional , Electroforesis en Gel Bidimensional , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Proteoma/química , Proteoma/metabolismo , Reproducibilidad de los Resultados , Elementos de RespuestaRESUMEN
We aimed to compare the effects of a personalized short-term high-intensity interval training (HIIT) vs. standard moderate intensity continuous training (MICT) on body fat percentage, abdominal circumference, BMI and maximal oxygen uptake (VO2max) in overweight volunteers. Twenty overweight sedentary volunteers (24.9 ± 2.9y; BMI: 26.1 ± 1 kgm-2) were randomly assigned to 2 groups, HIIT or MICT. HIIT trained 6 weeks (3-days/week), 40-min sessions as follows: 6-min warm-up, 20-min resistance training (RT) at 70% 1-RM, 8-min HIIT up to 90% of the predicted Maximal Heart Rate (HRmax), 6-min cool-down. MICT trained 6 weeks (3-days/week) 60-min sessions as follows: 6-min warm-up, 20-min RT at 70% 1-RM, 30-min MICT at 60-70% of the predicted HRmax, 4-min cool-down. Two-way ANOVA was performed in order to compare the efficacy of HIIT and MICT protocols, and no significant interaction between training x time was evidenced (p > 0.05), indicating similar effects of both protocols on all parameters analyzed. Interestingly, the comparison of Δ mean percentage revealed an improvement in VO2max (p = 0.05) together with a positive trend in the reduction of fat mass percentage (p = 0.06) in HIIT compared to MICT protocol. In conclusion, 6 weeks of personalized HIIT, with reduced training time (40 vs. 60 min)/session and volume of training/week, improved VO2max and reduced fat mass percentage more effectively compared to MICT. These positive results encourage us to test this training in a larger population.
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This narrative review aims to critically analyze the effects of exercise on health in aging. Here we discuss the main clinical and biomolecular modifications induced by long-term recreational football training in older subjects. In particular, the effects induced by long-term recreational football training on cardiovascular, metabolic and musculo-skeletal fitness, together with the modifications in the muscle expression of hallmarks related to oxidative metabolism, DNA repair and senescence suppression pathways and protein quality control mechanisms will be provided. All these topics will be debated also in terms of preventing non-communicable metabolic diseases, in order to achieve successful aging over time.
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Reparación del ADN , Ejercicio Físico , Fútbol Americano , Envejecimiento Saludable , Fútbol , Adulto , Humanos , Persona de Mediana EdadRESUMEN
Functional beverages represent a palatable and efficient way to hydrate and reintegrate electrolytes, carbohydrates, and other nutrients employed and/or lost during physical training and/or competitions. Bodily hydration during sporting activity is one of the best indicators of health in athletes and can be a limiting factor for sport performance. Indeed, dehydration strongly decreases athletic performance until it is a risk to health. As for other nutrients, each of them is reported to support athletes' needs both during the physical activity and/or in the post-workout. In this study, we review the current knowledge of macronutrient-enriched functional beverages in sport taking into account the athletes' health, sports performance, and recovery.
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Rendimiento Atlético/fisiología , Bebidas , Alimentos Funcionales/análisis , Deshidratación/fisiopatología , Ejercicio Físico/fisiología , Humanos , Nutrientes/análisis , Recuperación de la Función , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
Performance-enhancing drugs (PEDs) gained wide popularity not only among sportsmen but also among specific subsets of population, such as adolescents. Apart from their claimed effects on athletic performance, they are very appealing due to the body shaping effect exerted on fat mass and fat-free mass. Besides the "underestimated" massive misuse of PEDs, the short- as well as long-term consequences of such habits remain largely unrecognized. They have been strictly associated with serious adverse effects, but molecular mechanisms are yet to be elucidated. Here, we analyze the current understanding of the molecular effects of supraphysiological doses of doping agents in healthy biological systems, at genomic and proteomic levels, in order to define the molecular sensors of organ/tissue impairment, determined by their misuse. The focus is put on the anabolic androgenic steroids (AASs), specifically testosterone (T) and its most potent derivative dihydrotestosterone (DHT), and on the peptide hormones, specifically the growth hormone (GH) and the insulin-like growth factor-1 (IGF-1). A map of molecular targets is defined and the risk incidence for human health is taken into account.
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Doping en los Deportes , Hormona del Crecimiento/farmacología , Testosterona/farmacología , Apoptosis/efectos de los fármacos , Biomarcadores/análisis , Biomarcadores/química , Hormona del Crecimiento/efectos adversos , Humanos , Proteómica , Transducción de Señal/efectos de los fármacos , Testosterona/efectos adversosRESUMEN
We have examined the effects of an adenosine 3',5'-cyclic monophosphate (cAMP) analog on human aldolase C gene expression in the rat pheochromocytoma cell line PC12. Incubation for 4 h with 500 microM 8-Br-cAMP increased aldolase C mRNA expression 2.5-fold and the expression was still above basal level 24 h later. Using transient transfection experiments we demonstrate that the distal element D in the promoter region of the human aldolase C gene, which binds a transcriptional activator (NGFI-B), is involved in this regulation. NGFI-B mRNA and protein expression were promptly (15 min) increased after 8-Br-cAMP treatment and precedes aldolase C mRNA increase (30 min). After 4 h of 8-Br-cAMP treatment, the binding of NGFI-B protein to the distal element D in the distal promoter region was increased twofold and this correlates with the increased expression of the clone that contains distal element D. These results indicate that the distal element D in the promoter region of the human aldolase C gene is the target of a cAMP-dependent regulation pathway.
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AMP Cíclico/farmacología , Fructosa-Bifosfato Aldolasa/genética , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Animales , Cloranfenicol O-Acetiltransferasa/efectos de los fármacos , Cloranfenicol O-Acetiltransferasa/genética , Cloranfenicol O-Acetiltransferasa/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Expresión Génica/genética , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Células PC12 , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Receptores Citoplasmáticos y Nucleares , Receptores de Esteroides , Proteínas Recombinantes de Fusión/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Elementos de Respuesta/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Aldolase C is selectively expressed in the hippocampus and Purkinje cells in adult mammalian brain. The gene promoter regions governing cell-specific aldolase C expression are obscure. We show that aldolase C messenger expression in the hippocampus is restricted to CA3 neurons. The human distal promoter region (-200/-1200 bp) is essential for beta-galactosidase (beta-gal) expression in CA3 neurons and drives high stripe-like beta-gal expression in Purkinje cells. The 200 bp proximal promoter region is sufficient to drive low brain-specific and stripe-like beta-gal expression in Purkinje cells. Thus, the human aldolase C gene sequences studied drive endogenous-like expression in the brain.
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Fructosa-Bifosfato Aldolasa/genética , Regulación Enzimológica de la Expresión Génica , Hipocampo/enzimología , Operón Lac , Regiones Promotoras Genéticas , Células de Purkinje/enzimología , Animales , Encéfalo/citología , Encéfalo/enzimología , Fructosa-Bifosfato Aldolasa/metabolismo , Hipocampo/citología , Humanos , Hibridación in Situ , Isoenzimas/genética , Isoenzimas/metabolismo , Ratones , Ratones Transgénicos , Modelos Genéticos , Neuronas/enzimología , Células de Purkinje/citología , ARN Mensajero/metabolismo , beta-Galactosidasa/metabolismoRESUMEN
BACKGROUND: Significant and sustained excess weight loss (EWL) appears to reduce the risk of obesity-related comorbidities (insulin resistance, hyperlipidemia, and inflammation), but this has been primarily shown in adult diabetic obese patients. We evaluated whether the EWL obtained 3 years after laparoscopic adjustable gastric banding (LAGB) improves the metabolic phenotype in nondiabetic morbidly obese (NDMO) individuals from south Italy. METHODS: Serum and subcutaneous adipose tissue (SAT) samples from 20 obese individuals (median BMI=41.5 kg/m(2)) before (T0) and after LAGB (T1) and from 10 controls (median BMI=22.8 kg/m(2)) were taken. Serum leptin, adiponectin, C reactive protein (CRP), and main analyte levels were evaluated by routine methods or immunoassay. In SAT, adipocyte size was measured by hematoxylin/eosin staining, cluster of differentiation 68 (CD68) macrophage infiltration marker by immunohistochemistry, and adiponectin, adiponectin receptors 1 and 2, and interleukin 6 (IL6) messenger RNAs by qRT-PCR. RESULTS: The average EWL was 66.7 %, and CRP, triglycerides, hepatic markers, leptin levels, homeostasis model assessment, and the leptin/adiponectin ratio were lower (p<0.05) at T1 than at T0. The expression of small adipocytes and adiponectin was increased (p<0.05), and inflammation markers (CD68 and IL6) decreased (p<0.05) at T1 vs. T0. At linear regression multivariate analysis, over 90 % (R (2)=0.905) of EWL (dependent variable) was explained by CD68, adiponectinemia, triglyceridemia, CRP, and total protein levels. CONCLUSIONS: The EWL obtained 3 years after LAGB resulted in an improvement of lipid metabolism and a reduction of inflammation in NDMO patients, thereby decreasing the risk of obesity-associated diseases.
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Diabetes Mellitus Tipo 2 , Inflamación/fisiopatología , Obesidad Mórbida/cirugía , Grasa Subcutánea/fisiopatología , Adulto , Estudios de Casos y Controles , Colesterol/sangre , Femenino , Gastroplastia/métodos , Humanos , Inflamación/prevención & control , Italia , Masculino , Obesidad Mórbida/sangre , Pérdida de PesoRESUMEN
The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity.