RESUMEN

Marathon runners, subjected to intense training regimens and prolonged, exhaustive exercises, often experience a compromised immune response. Probiotic supplementation has emerged as a potential remedy to mitigate the impact of prolonged exercise on athletes. Consequently, this study sought to assess the influence of probiotic supplementation on monocyte functionality both before and after the official marathon race. Twenty-seven runners were randomly and double-blindly assigned to two groups: placebo (n 13) and probiotic (PRO) (n 14). Over 30 d, both groups received supplements - placebo sachets containing maltodextrin (5 g/d) and PRO sachets containing 1 × 1010 colony-forming unit Lactobacillus acidophilus and 1 × 1010 colony-forming unit Bifidobacterium bifidum subsp. lactis. Blood samples were collected, and immunological assays, including phagocytosis, hydrogen peroxide production, cytokine levels and monocyte immunophenotyping, were conducted at four different intervals: baseline (start of supplementation/30 d pre-marathon), 24 h-before (1 d pre-marathon), 1 h-after (1 h post-marathon) and 5 d-after (5 d post-marathon). Monocyte populations remained consistent throughout the study. A notable increase in phagocytosis was observed in the PRO group after 30 d of supplementation. Upon lipopolysaccharide stimulation, both PRO and placebo groups exhibited decreased IL-8 production. However, after the marathon race, IL-15 stimulation demonstrated increased levels of 5 d-after, while IL-1-ß, IL-8, IL-10, IL-15 and TNF-α varied across different intervals, specifically within the PRO group. Probiotic supplementation notably enhanced the phagocytic capacity of monocytes. However, these effects were not sustained post-marathon.

Asunto(s)

Suplementos Dietéticos , Carrera de Maratón , Monocitos , Fagocitosis , Probióticos , Humanos , Fagocitosis/efectos de los fármacos , Probióticos/administración & dosificación , Probióticos/farmacología , Monocitos/metabolismo , Monocitos/inmunología , Método Doble Ciego , Masculino , Adulto , Carrera de Maratón/fisiología , Citocinas/metabolismo , Citocinas/sangre , Femenino , Lactobacillus acidophilus , Bifidobacterium bifidum/fisiología , Persona de Mediana Edad , Carrera/fisiología , Atletas

RESUMEN

BACKGROUND: The term immunometabolism describes cellular and molecular metabolic processes that control the immune system and the associated immune responses. Acute exercise and regular physical activity have a substantial influence on the metabolism and the immune system, so that both processes are closely associated and influence each other bidirectionally. SCOPE OF REVIEW: We limit the review here to focus on metabolic phenotypes and metabolic plasticity of T cells and macrophages to describe the complex role of acute exercise stress and regular physical activity on these cell types. The metabolic and immunological consequences of the social problem of inactivity and how, conversely, an active lifestyle can break this vicious circle, are then described. Finally, these aspects are evaluated against the background of an aging society. MAJOR CONCLUSIONS: T cells and macrophages show high sensitivity to changes in their metabolic environment, which indirectly or directly affects their central functions. Physical activity and sedentary behaviour have an important influence on metabolic status, thereby modifying immune cell phenotypes and influencing immunological plasticity. A detailed understanding of the interactions between acute and chronic physical activity, sedentary behaviour, and the metabolic status of immune cells, can help to target the dysregulated immune system of people who live in a much too inactive society.

Asunto(s)

Ejercicio Físico , Linfocitos T , Metabolismo Energético , Humanos , Macrófagos/metabolismo , Conducta Sedentaria

RESUMEN

Probiotic supplementation arises as playing an immune-stimulatory role. High-intensity and -volume exercise can inhibit immune cell function, which threatens athletic performance and recovery. We hypothesized that 30 days of probiotic supplementation could stabilize the immune system of athletes preventing immune suppression after a marathon race. Twenty-seven male marathonists were double-blinded randomly into probiotic (Bifidobacterium-animalis-subsp.-Lactis (10 × 109) and Lactobacillus-Acidophilus (10 × 109) + 5 g of maltodextrin) and placebo (5 g of maltodextrin) group. They received 30 sachets and supplemented 1 portion/day during 30 days before the race. Blood were collected 30 days before (rest), 1 day before (pre), 1 h after (post) and 5 days after the race (recovery). Both chronic and acute exercise modulated a different T lymphocyte population (CD3+CD4-CD8- T-cells), increasing pre-race, decreasing post and returning to rest values at the recovery. The total number of CD8 T cell and the memory subsets statistically decreased only in the placebo group post-race. Pro-inflammatory cytokine production by stimulated lymphocytes decreased in the probiotic group after the supplementation period. 30 days of probiotic supplementation maintained CD8 T cell and effector memory cell population and played an immunomodulatory role in stimulated lymphocytes. Both, training and marathon modulated a non-classical lymphocyte population regardless of probiotic supplementation.

Asunto(s)

Rendimiento Atlético/fisiología , Linfocitos T CD8-positivos/inmunología , Suplementos Dietéticos , Recuento de Linfocitos , Carrera de Maratón/fisiología , Probióticos/administración & dosificación , Probióticos/farmacología , Adulto , Bifidobacterium animalis , Citocinas/metabolismo , Método Doble Ciego , Humanos , Inmunomodulación/inmunología , Mediadores de Inflamación/metabolismo , Lactobacillus acidophilus , Masculino , Adulto Joven

RESUMEN

The aim of this study was to analyze the metabolic and molecular profile according to physical fitness status (Low or High VO2max) and its impacts on peripheral and cellular inflammatory responses in healthy men. First (Phase I), inflammatory profile (TNF-α, IL-6, IL-10) was analyzed at baseline and post-acute exercise sessions performed at low (< 60% VO2max) and high (> 90% VO2max) intensities considering the individual endotoxin concentrations. Next (Phase II), monocyte cell cultures were treated with LPS alone or associated with Rosiglitazone (PPAR-γ agonist drug) to analyze cytokine production and gene expression. Monocyte subsets were also evaluated by flow cytometry. A positive relationship was observed between LPS concentrations and oxygen uptake (VO2max) (r = 0.368; p = 0.007); however, in the post-exercise an inverse correlation was found between LPS variation (Δ%) and VO2max (r = -0.385; p = 0.004). With the low-intensity exercise session, there was inverse correlation between LPS and IL-6 concentrations post-exercise (r = -0.505; p = 0.046) and a positive correlation with IL-10 in the recovery (1 h post) (r = 0.567; p = 0.011), whereas with the high-intensity exercise an inverse correlation was observed with IL-6 at pre-exercise (r = -0.621; p = 0.013) and recovery (r = -0.574; p = 0.016). When monocyte cells were treated with LPS, High VO2max individuals showed higher PPAR-γ gene expression whereas Low VO2max individuals displayed higher IL-10 production. Additionally, higher TLR-4, IKK1, and PGC-1α gene expression were observed in the High VO2max group than Low VO2max individuals. In conclusion, even with elevated endotoxemia, individuals with High VO2max exhibited higher IL-6 concentration in peripheral blood post-acute aerobic exercise and lower IL-10 concentration during recovery (1 h post-exercise). The anti-inflammatory effects linked with exercise training and physical fitness status may be explained by a greater gene expression of IKK1, TLR-4, and PGC-1α, displaying an extremely efficient cellular framework for the PPAR-γ responses.

Asunto(s)

Ejercicio Físico/fisiología , Lipopolisacáridos/metabolismo , Consumo de Oxígeno/fisiología , PPAR gamma/sangre , PPAR gamma/metabolismo , Aptitud Física/fisiología , Adulto , Células Cultivadas , Endotoxemia/sangre , Humanos , Hipoglucemiantes/farmacología , Interleucina-10/sangre , Interleucina-6/sangre , Leucocitos Mononucleares/citología , Lipopolisacáridos/sangre , Masculino , PPAR gamma/agonistas , Rosiglitazona/farmacología , Factor de Necrosis Tumoral alfa/sangre

RESUMEN

The aim of this study was to evaluate the inflammatory (peripheral and lipopolysaccharide (LPS)-stimulated released from whole blood) and metabolic (glucose and insulin) profile of inactive obese men in response to two isoenergetic models of aerobic exercise training (~300  kcal each exercise session). Twenty-two participants (28.7 ± 1.6 years; BMI = 34.4 ± 0.1 kg/m2) were randomized into two groups: I) HIIT: high-intensity interval training (10× 1 bout: 1 min - 100% Maximal Aerobic Velocity) or II) MICT: moderate-intensity continuous training (65% Maximal Aerobic Velocity; kcal equal to HIIT). Both groups trained three times per week for 6-weeks. Fasting blood samples were collected before and 0, 30, and 60 min after exercise during the first and last training sessions for evaluation of: I) MIP-1ɑ, insulin, glucose, visceral and subcutaneous fat depots, oral glucose tolerance test, and homeostatic model assessment of insulin resistance (HOMA-IR) index; II) Peripheral (TNF-α, IL-6, and IL-10) and LPS-stimulated release of TNF-α and IL-10 were analyzed before, 0, and 60 min after sessions. IL-6 concentration remained elevated up to 60-min after the acute exercise session (p < 0.001), and IL-10 concentration was higher after 30 and 60-min (p = 0.001) compared to rest, independent of training period and protocol. AUC of IL-10 presented effect of type of training (p = 0.023) with MICT group showed significantly higher values than the HIIT. The ex-vivo assay showed higher IL-10 secretion in response to LPS immediately (p = 0.003) after both acute MICT and HIIT exercise sessions, independent of training period. Fifteen subjects presented decreased HOMA-IR after 6-weeks and seven presented an increase in this index. When we excluded the two least responsive subjects, it was possible to observe a decrease in HOMA-IR (p = 0.020) after training. Taken together, our results suggest that both HIIT and MICT (with same energy expenditure) promote similar effects on HOMA-IR and led to elevations in IL-10 production in LPS-stimulated whole blood, suggesting that leukocytes had an enhanced ability to secrete anti-inflammatory cytokines after the exercise bout.

Asunto(s)

Entrenamiento de Intervalos de Alta Intensidad , Interleucina-10/biosíntesis , Leucocitos/metabolismo , Lipopolisacáridos/farmacología , Obesidad Infantil/metabolismo , Adolescente , Adulto , Humanos , Masculino , Obesidad Infantil/patología

RESUMEN

Circadian rhythm is essential for cellular regulation of physiological, metabolic, and immune functions. Perturbations of circadian rhythms have been correlated with increased susceptibility to cancer and poor prognosis in the cancer treatment. Our aim is to investigate the role of doxorubicin (DOX) treatment on clock genes expression and inflammation in intraperitoneal macrophages and the antitumoral response. METHODS: Macrophages were extracted from intraperitoneal cavity of mice without or with Lewis lung carcinoma (LLC) and treated with DOX totaling four groups (CTL, LLC, LLC+DOX and DOX) and analyzes of clock genes in six time points (ZT02, ZT06, ZT10, ZT14, ZT18 AND ZT22). Intraperitoneal macrophages cell culture was stimulated with LPS and DOX and clock genes and inflammatory profile were analyzed. In tumor were analyzed macrophages markers. RESULTS: The expression of F4/80 (ZT22) and CD11c (ZT06) tumor tissue was significantly differed between LLC and LCC+DOX groups. In the intraperitoneal macrophages, DOX increased Clock (ZT10), Rev-Erbα (ZT18 and ZT22) and Per2 expressions (ZT18); in the LLC+DOX group was increased Bmal1 (ZT10), Per2 (ZT18) and NF-kB (ZT22) expressions; IL-6 expression increased in the LCC group (ZT02). In intraperitoneal macrophages cell culture stimulated with DOX and LPS after 24 h decreased Clock and Per1. DOX causes depression after 6 and 24 h in TNF-α content and Per2 gene expression after 24 h IL-1ß expression was reduced also. CONCLUSION: DOX treatment in vivo disrupted cytokine and clock genes expression in intraperitoneal macrophages suppressing immune response. Moreover, macrophages cultured with DOX had decreased expression of LPS-stimulated inflammatory cytokines.

Asunto(s)

Proteínas CLOCK/genética , Carcinoma Pulmonar de Lewis/metabolismo , Ritmo Circadiano/efectos de los fármacos , Citocinas/metabolismo , Doxorrubicina/farmacología , Inflamación/metabolismo , Macrófagos/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor , Proteínas CLOCK/metabolismo , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/patología , Proliferación Celular , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/patología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Células Tumorales Cultivadas

RESUMEN

Many lifestyle-related diseases, such as obesity and cigarette smoke-induced pulmonary diseases, are associated with chronic systemic inflammation, which has been shown to contribute to the disease initiation and progression, and also for co-morbidities of these diseases. While the source of inflammation in obese subjects is suggested to be mainly the visceral adipose tissue, smoke-induced inflammation originates in the pulmonary system. Here, chronic cigarette smoking induces oxidative stress, resulting in severe cellular damage. During obesity, metabolic stress pathways in adipocytes induce inflammatory cascades which are also accompanied by fibrotic processes and insulin resistance. In both diseases, local inflammatory signals induce progressive immune cell infiltration, release of cytokines and a subsequent spill-over of inflammation to the systemic circulation. Exercise training represents an effective therapeutic and immune regulating strategy for both obese patients, as well as for patients with smoke induced pulmonary inflammation. While the immuneregulating impact of exercise might primarily depend on the disease state, patients with pulmonary inflammation seem to be less responsive to exercise therapy. The current review tries to identify similarities and differences between inflammatory processes, and the consequences for the immunoregulatory effects of exercise as a therapeutic agent.

Asunto(s)

Ejercicio Físico , Inflamación/patología , Obesidad/patología , Fumar/efectos adversos , Humanos , Inflamación/inmunología , Obesidad/inmunología , Humo/efectos adversos , Nicotiana

RESUMEN

Aging is one of the risk factors for the development of low-grade inflammation morbidities, such as several types of cancer and neurodegenerative diseases, due to changes in the metabolism, hormonal secretion, and immunosenescence. The senescence of the immune system leads to improper control of infections and tissue damage increasing age-related diseases. One of the mechanisms that maintain cellular homeostasis is autophagy, a cell-survival mechanism, and it has been proposed as one of the most powerful antiaging therapies. Regular exercise can reestablish autophagy, probably through AMP-activated protein kinase activation, and help in reducing the age-related senescence diseases. Therefore, in this study, we discuss the effects of exercise training in immunosenescence and autophagy, preventing the two main age-related disease, cancer and neurodegeneration.

RESUMEN

The immune system plays a key role in controlling infections, repairing injuries, and restoring homeostasis. Immune cells are bioenergetically expensive during activation, which requires a tightly regulated control of the metabolic pathways, which is mostly regulated by two cellular energy sensors: Adenosine monophosphate-activated protein kinase and mammalian target of rapamycin. The activation and inhibition of this pathways can change cell subtype differentiation. Exercise intensity and duration and nutrient availability (especially glucose and glutamine) tightly regulate immune cell differentiation and function through Adenosine monophosphate-activated protein kinase and mammalian target of rapamycin signaling. Herein, we discuss the innate and adaptive immune-cell metabolism and how they can be affected by exercise and nutrients.

Asunto(s)

Ejercicio Físico/fisiología , Sistema Inmunológico/enzimología , Nutrientes/farmacocinética , Disponibilidad Biológica , Diferenciación Celular/inmunología , Proteínas Quinasas Dependientes de AMP Cíclico/inmunología , Glucosa/farmacocinética , Glutamina/farmacocinética , Humanos , Transducción de Señal/inmunología , Serina-Treonina Quinasas TOR/inmunología

RESUMEN

BACKGROUND: Exercise is a powerful tool for prevention and treatment of many conditions related to the cardiovascular system and also chronic low-grade inflammation. Peroxisome proliferator-activated receptors γ (PPARγ) exerts an import role on the regulation of metabolic profile and subsequent inflammatory response, especially in macrophages. PURPOSE: To investigate the effects of 8-week moderate-exercise training on metabolic and inflammatory parameters in mice with PPARγ deficiency in myeloid cells. METHODS: Twelve-week old mice bearing PPARγ deletion exclusively in myeloid cells (PPARγlox/lox Lys Cre -/+ , knockout [KO]) and littermate controls (PPARγlox/lox Lys Cre -/- , wild type [WT]) were submitted to 8-week exercise training (treadmill running at moderate intensity, 5 days/week). Animals were evaluated for food intake, glucose homeostasis, serum metabolites, adipose tissue and peritoneal macrophage inflammation, and basal and stimulated cytokine secretion. RESULTS: Exercise protocol did not improve glucose metabolism or adiponectin concentrations in serum of KO mice. Moreover, the absence of PPARγ in macrophages exacerbated the proinflammatory profile in sedentary mice. Peritoneal cultured cells had higher tumor necrosis factor-α (TNF-α) secretion in nonstimulated and lipopolysaccharide (LPS)-stimulated conditions and higher Toll-4 receptor (TLR4) gene expression under LPS stimulus. Trained mice showed reduced TNF-α content in adipose tissue independently of the genotype. M2 polarization ability was impaired in KO peritoneal macrophages after exercise training, while adipose tissue-associated macrophages did not present any effect by PPARγ ablation. CONCLUSION: Overall, PPARγ seems necessary to maintain macrophages appropriate response to inflammatory stimulus and macrophage polarization, affecting also whole body lipid metabolism and adiponectin profile. Exercise training showed as an efficient mechanism to restore the immune response impaired by PPARγ deletion in macrophages.

Asunto(s)

Plasticidad de la Célula , Metabolismo Energético , Mediadores de Inflamación/metabolismo , Macrófagos Peritoneales/metabolismo , PPAR gamma/deficiencia , Condicionamiento Físico Animal/métodos , Adiponectina/sangre , Tejido Adiposo/metabolismo , Animales , Células Cultivadas , Eliminación de Gen , Lípidos/sangre , Macrófagos Peritoneales/inmunología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , PPAR gamma/genética , Fenotipo , Resistencia Física , Factores de Tiempo

RESUMEN

Doxorubicin (DX) is a chemotherapeutic drug that is used in clinical practice that promotes deleterious side effects in non-tumor tissues such as adipose tissue. We showed that DX leads to extensive damage in adipose tissue via a disruption in 5'-adenosine monophosphate-activated protein kinase (AMPK) and PPAR-gamma signaling. Thus, we investigated whether co-treatment with the biguanide drug metformin (MET) could prevent the side effects of DX through the activation of AMPK in adipose tissue. The goal of the present study was to verify the effects of DX and adjuvant MET treatment in subcutaneous adipose tissue (SAT) and to determine whether MET could protect against chemotherapy-induced side effects. C57/BL6 mice received DX hydrochloride (2.5 mg/kg) intraperitoneally 2 times per week for 2 weeks (DX), concomitantly or not, with MET administration (300 mg/kg oral daily) (DX + MET). The control group (CTRL) was pair-fed according to the food consumption of the DX group. After euthanasia, adipose tissue fat pads were collected, and SAT was extracted so that adipocytes could be isolated. Glucose uptake was then measured, and histological, gene, and protein analyses were performed. One-way analysis of variance was also performed, and significance was set to 5%. DX reduced retroperitoneal fat mass and epididymal pads and decreased glycemia. In cultured primary subcutaneous adipocytes, mice in the DX group had lower glucose uptake when stimulated with insulin compared with mice in the CTRL group. Adipocytes in the DX group exhibited a reduced area, perimeter, and diameter; decreased adiponectin secretion; and decreased fatty acid synthase gene expression. SAT from MET-treated mice also showed a reduction in collagen deposition. Treatment with MET prevented fibrosis and restored glucose uptake in SAT after insulin stimulation, yet the drug was unable to prevent other side effects of DX such as tissue loss and inflammatory response.

RESUMEN

The study aimed to evaluate the metabolic and inflammatory effects of short-term treatments (10 days) with metformin (MET) on the NAFLD caused by a high-fat diet (HFD) in C57BL/6 mice. After the treatment, histological liver slices were obtained, hepatocytes and macrophages were extracted and cultured with phosphate buffered saline, LPS (2.5 µg/mL) and MET (1 µM) for 24 h. Cytokine levels were determined by ELISA. NAFLD caused by the HFD was partially reduced by MET. The lipid accumulation induced by the HFD was not associated with liver inflammation; however, MET seemed to promote pro-inflammatory effects in liver, since it increased hepatic concentration of IL-1ß, TNF-α, IL-6, MCP-1 and IFN-γ. Similarly, MET increased the concentration of IL-1ß, IL-6 in hepatocyte cultures. However, in macrophages culture, MET lowered levels of IL-1ß, IL-6 and TNF-α stimulated by LPS. Overall, MET reduced liver NAFLD but promoted hepatocyte increase in pro-inflammatory cytokines, thus, leading to liver inflammation.

Asunto(s)

Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Metformina/farmacología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Dieta Alta en Grasa , Ensayo de Inmunoadsorción Enzimática , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Inflamación/patología , Lípidos/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/patología

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) play a major role in metabolism and inflammatory control. Exercise can modulate PPAR expression in skeletal muscle, adipose tissue, and macrophages. Little is known about the effects of PPAR-α in metabolic profile and cytokine secretion after acute exercise in macrophages. In this context, the aim of this study was to understand the influence of PPAR-α on exercise-mediated immune metabolic parameters in peritoneal macrophages. Mice C57BL/6 (WT) and PPAR-α knockout (KO) were examined in non-exercising control (n = 4) or 24 hours after acute moderate exercise (n = 8). Metabolic parameters (glucose, non-esterified fatty acids, total cholesterol [TC], and triacylglycerol [TG]) were assessed in serum. Cytokine concentrations (IL-1ß, IL-6, IL-10, TNF-α, and MCP-1) were measured from peritoneal macrophages cultured or not with LPS (2.5 µg/mL) and Rosiglitazone (1 µM). Exercised KO mice exhibited low glucose concentration and higher TC and TG in serum. At baseline, no difference in cytokine production between the genotypes was observed. However, IL-1ß was significantly higher in KO mice after LPS stimulus. IL-6 and IL-1ß had increased concentrations in KO compared with WT, even after exercise. MCP-1 was not restored in exercised KO LPS group. Rosiglitazone was not able to reduce proinflammatory cytokine production in KO mice at baseline level or associated with exercise. Acute exercise did not alter mRNA expression in WT mice. CONCLUSION: PPAR-α seems to be needed for metabolic glucose homeostasis and anti-inflammatory effect of acute exercise. Its absence may induce over-expression of pro-inflammatory cytokines in LPS stimulus. Moreover, moderate exercise or PPAR-γ agonist did not reverse this response.

Asunto(s)

Inflamación/metabolismo , PPAR alfa/deficiencia , Condicionamiento Físico Animal , Animales , Colesterol/sangre , Glucosa/metabolismo , Homeostasis , Inflamación/inducido químicamente , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , PPAR alfa/genética , Triglicéridos/sangre

RESUMEN

BACKGROUND: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. OBJECTIVE: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice. METHODS: C57BL6 and PPARα knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high-fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid. RESULTS: Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP-1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF-21 and stimulated the expression of PPARα. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF-21 in liver of PPARα KO mice. CONCLUSIONS: In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPARα. J. Cell. Physiol. 232: 2168-2177, 2017. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Proteínas Quinasas Activadas por AMP/metabolismo , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos Monoinsaturados/farmacología , Hígado Graso/tratamiento farmacológico , Hígado/efectos de los fármacos , PPAR alfa/metabolismo , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Activación Enzimática , Hígado Graso/enzimología , Hígado Graso/genética , Hígado Graso/patología , Factores de Crecimiento de Fibroblastos/metabolismo , Predisposición Genética a la Enfermedad , Glucoquinasa/metabolismo , Glucosa/metabolismo , Hipoglucemiantes/farmacología , Insulina/farmacología , Hígado/enzimología , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , PPAR alfa/deficiencia , PPAR alfa/genética , Fenotipo , Fosforilación , Transducción de Señal/efectos de los fármacos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Factores de Tiempo

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases today, and may progress to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Some studies have shown the beneficial effects of aerobic exercise on reversing NAFLD. To verify whether chronic aerobic exercise improves the insulin resistance, liver inflammation, and steatohepatitis caused by a high fat diet (HF) and whether PPARα is involved in these actions. C57BL6 wild type (WT) and PPAR-α knockout (KO) mice were fed with a standard diet (SD) or HF during 12 weeks; the HF mice were trained on a treadmill during the last 8 weeks. Serum glucose and insulin tolerances, serum levels of aspartate aminotransferase, hepatic content of triacylglycerol, cytokines, gene expression, and protein expression were evaluated in all animals. Chronic exposure to HF diet increased triacylglycerol accumulation in the liver, leading to NAFLD, increased aminotransferase in the serum, increased peripheral insulin resistance, and higher adiposity index. Exercise reduced all these parameters in both animal genotypes. The liver lipid accumulation was not associated with inflammation; trained KO mice, however, presented a huge inflammatory response that was probably caused by a decrease in PPAR-γ expression. We conclude that exercise improved the damage caused by a HF independently of PPARα, apparently by a peripheral fatty acid oxidation in the skeletal muscle. We also found that the absence of PPARα together with exercise leads to a decrease in PPAR-γ and a huge inflammatory response. J. Cell. Physiol. 232: 1008-1019, 2017. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Progresión de la Enfermedad , Inflamación/tratamiento farmacológico , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , PPAR alfa/deficiencia , Condicionamiento Físico Animal , Tiazolidinedionas/uso terapéutico , Animales , Peso Corporal , Ayuno/sangre , Inflamación/sangre , Inflamación/complicaciones , Inflamación/genética , Lípidos/sangre , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/genética , Tamaño de los Órganos , PPAR alfa/metabolismo , Fosforilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Rosiglitazona

RESUMEN

White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances. Chronic exercise is a nonpharmacological therapy employed in several chronic diseases and shows an anti-inflammatory effect through the regulation of the cytokine network. In this review, we address the potential mechanisms by which the aerobic physical exercise modulate the production and release of inflammatory adipokines, as well as the inflammation-lipolysis axis in WAT, with special focus in the therapeutic role of exercise in obesity-associated insulin resistance and cancer cachexia.

Asunto(s)

Caquexia/fisiopatología , Ejercicio Físico , Inflamación , Neoplasias/fisiopatología , Obesidad/fisiopatología , Tejido Adiposo Blanco/inmunología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/fisiopatología , Caquexia/etiología , Caquexia/inmunología , Caquexia/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Humanos , Neoplasias/complicaciones , Neoplasias/inmunología , Neoplasias/metabolismo , Obesidad/inmunología , Obesidad/metabolismo

RESUMEN

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-α dependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF ����B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.

Asunto(s)

Ácidos Grasos Monoinsaturados/uso terapéutico , PPAR alfa/metabolismo , Animales , Western Blotting , Dieta Alta en Grasa/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Resistencia a la Insulina , Interleucina-12 , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ácido Oléico/metabolismo , Ácido Oléico/uso terapéutico , PPAR alfa/deficiencia , PPAR alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

BACKGROUND: Artistic Gymnastics is a sport where athletes are frequently fatigued. One element that might influence this aspect is carbohydrate, an important energy substrate for the muscles and the CNS. Our goal was to investigate the influence of fatigue over artistic gymnastics athlete's performance and the effects of a carbohydrate supplementation on their performance. METHODS: We evaluated 15 athletes divided in 2 groups (control and fatigue) from 12 to 14 years old in two different experimental days. On the first day (water day), they did 5 sets of exercises on the balance beam (experimental protocol) ingesting only water, CG (control group) warmed up before the experimental protocol and FG (fatigue group) did a fatigue circuit, warm up exercises and then the experimental protocol. On the second day (carbohydrate day), we used the same protocol but CG ingested a sugar free flavored juice and FG ingested a 20% concentration maltodextrin solution before the protocol on the balance beam. RESULTS: We observed a greater number of falls from the balance beam from the FG on the first day (5.40 ± 1.14 FG vs 3.33 ± 1.37 CG; p = 0.024) and a decrease in the number of falls on the second day (2.29 ± 1.25 FG water day vs 5.40 ± 1.14 FG carbohydrate day; p = 0.0013). Carbohydrate solution was able to supply muscle demands and improve the athlete's focus showed by the reduced number of falls.