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1.
Cell Mol Life Sci ; 80(5): 122, 2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37052684

RESUMEN

OBJECTIVE: Intriguingly, hyperinsulinemia, and hyperglycemia can predispose insulin resistance, obesity, and type 2 diabetes, leading to metabolic disturbances. Conversely, physical exercise stimulates skeletal muscle glucose uptake, improving whole-body glucose homeostasis. Therefore, we investigated the impact of short-term physical activity in a mouse model (Slc2a4+/-) that spontaneously develops hyperinsulinemia and hyperglycemia even when fed on a chow diet. METHODS: Slc2a4+/- mice were used, that performed 5 days of endurance or strength exercise training. Further analysis included physiological tests (GTT and ITT), skeletal muscle glucose uptake, skeletal muscle RNA-sequencing, mitochondrial function, and experiments with C2C12 cell line. RESULTS: When Slc2a4+/- mice were submitted to the endurance or strength training protocol, improvements were observed in the skeletal muscle glucose uptake and glucose metabolism, associated with broad transcriptomic modulation, that was, in part, related to mitochondrial adaptations. The endurance training, but not the strength protocol, was effective in improving skeletal muscle mitochondrial activity and unfolded protein response markers (UPRmt). Moreover, experiments with C2C12 cells indicated that insulin or glucose levels could contribute to these mitochondrial adaptations in skeletal muscle. CONCLUSIONS: Both short-term exercise protocols were efficient in whole-body glucose homeostasis and insulin resistance. While endurance exercise plays an important role in transcriptome and mitochondrial activity, strength exercise mostly affects post-translational mechanisms and protein synthesis in skeletal muscle. Thus, the performance of both types of physical exercise proved to be a very effective way to mitigate the impacts of hyperglycemia and hyperinsulinemia in the Slc2a4+/- mouse model.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Resistencia a la Insulina , Ratones , Animales , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Músculo Esquelético/metabolismo , Hiperglucemia/genética , Hiperglucemia/metabolismo , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo
2.
J Physiol ; 600(4): 797-813, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33450053

RESUMEN

KEY POINTS: Time-restricted feeding (TRF, in which energy intake is restricted to 8 h/day during the dark phase) alone or combined with aerobic exercise (AE) training can prevent weight gain and metabolic disorders in Swiss mice fed a high-fat diet. The benefits of TRF combined with AE are associated with improved hepatic metabolism and decreased hepatic lipid accumulation. TRF combined with AE training increased fatty acid oxidation and decreased expression of lipogenic and gluconeogenic genes in the liver of young male Swiss mice. TRF combined with AE training attenuated the detrimental effects of high-fat diet feeding on the insulin signalling pathway in the liver. ABSTRACT: Time-restricted feeding (TRF) or physical exercise have been shown to be efficient in the prevention and treatment of metabolic disorders; however, the additive effects of TRF combined with aerobic exercise (AE) training on liver metabolism have not been widely explored. In this study TRF (8 h in the active phase) and TRF combined with AE (TRF+Exe) were compared in male Swiss mice fed a high-fat diet, with evaluation of the effects on insulin sensitivity and expression of hepatic genes involved in fatty acid oxidation, lipogenesis and gluconeogenesis. As in previous reports, we show that TRF alone (eating only between zeitgeber time 16 and 0) was sufficient to reduce weight and adiposity gain, increase fatty acid oxidation and decrease lipogenesis genes in the liver. In addition, we show that mice of the TRF+Exe group showed additional adaptations such as increased oxygen consumption ( V̇O2${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ ), carbon dioxide production ( V̇CO2${\dot V_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ ) and production of ketone bodies (ß-hydroxybutyrate). Also, TRF+Exe attenuated the negative effects of high-fat diet feeding on the insulin signalling pathway (insulin receptor, insulin receptor substrate, Akt), and led to increased fatty acid oxidation (Ppara, Cpt1a) and decreased gluconeogenic (Fbp1, Pck1, Pgc1a) and lipogenic (Srebp1c, Cd36) gene expression in the liver. These molecular results were accompanied by increased glucose metabolism, lower serum triglycerides and reduced hepatic lipid content in the TRF+Exe group. The data presented in this study show that TRF alone has benefits but TRF+Exe has additive benefits and can mitigate the harmful effects of consuming a high-fat diet on body adiposity, liver metabolism and glycaemic homeostasis in young male Swiss mice.


Asunto(s)
Resistencia a la Insulina , Enfermedades Metabólicas , Animales , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Masculino , Enfermedades Metabólicas/metabolismo , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Aumento de Peso
3.
Clin Exp Pharmacol Physiol ; 49(10): 1072-1081, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35690890

RESUMEN

Obesity is associated with low-grade inflammation and disturbances in hepatic metabolism. This study aimed to investigate the effects of resistance exercise on inflammatory signalling related to IκB kinase (IKK) ɛ protein (IKKɛ) and on hepatic fat accumulation in obese mice. Male Swiss mice were distributed into three groups: control (CTL) fed with standard chow; obese (OB) mice induced by a high-fat diet (HFD); obese exercised (OB + RE) mice fed with HFD and submitted to a resistance exercise training. The resistance exercise training protocol consisted of 20 sets/3 ladder climbs for 8 weeks, three times/week on alternate days. The training overload was equivalent to 70% of the maximum load supported by the rodent. Assays were performed to evaluate weight gain, hepatic fat content, fasting glucose, insulin sensitivity, IKKɛ phosphorylation and proteins related to insulin signalling and lipogenesis in the liver. Mice that received the high-fat diet showed greater adiposity, impaired insulin sensitivity, increased fasting glucose and increased hepatic fat accumulation. These results were accompanied by an increase in IKKɛ phosphorylation and lipogenesis-related proteins such as cluster of differentiation 36 (CD36) and fatty acid synthase (FAS) in the liver of obese mice. In contrast, exercised mice showed lower body weight and adiposity evolution throughout the experiment. In addition, resistance exercise suppressed the effects of the high-fat diet by reducing IKKɛ phosphorylation and hepatic fat content. In conclusion, resistance exercise training improves hepatic fat metabolism and glycaemic homeostasis, which are, at least in part, linked to the anti-inflammatory effect of reduced IKKɛ phosphorylation in the liver of obese mice.


Asunto(s)
Adiposidad , Quinasa I-kappa B , Hígado , Obesidad , Entrenamiento de Fuerza , Animales , Dieta Alta en Grasa/efectos adversos , Glucosa/metabolismo , Humanos , Quinasa I-kappa B/metabolismo , Resistencia a la Insulina , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/metabolismo , Fosforilación
4.
Cytokine ; 137: 155306, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33010727

RESUMEN

PURPOSE: Interleukin-15 (IL-15) is a myokine that has been proposed to modulate skeletal muscle and adipose tissue mass, as well as insulin sensitivity. However, the evidence suggesting a role for IL-15 in improving whole-body insulin sensitivity and decreasing adiposity comes mainly from studies using supraphysiological levels of this cytokine. This study examined the effect of a short-term exercise training protocol on the protein content of IL-15, it's signaling pathway, and glucose tolerance in aged rats. METHODS: Fourteen Wistar rats were divided into Young Sedentary (Young, n = 4); Old Sedentary (Old, n = 5); Old Exercise (Old.Exe, n = 5) groups. The animals from the exercised group were submitted to a short-term physical exercise protocol for five days. At the end of physical training and after 16 h of the last exercise session, the animals were euthanized, and tissue collection was done. RESULTS: Physical exercise decreased epididymal and mesenteric fat mass and promoted positive effects on glucose tolerance and insulin sensitivity. Muscle IL-15 protein levels were not changed following the short-term physical exercise training with no alterations in the post-exercise IL-15-JAK/STAT signaling pathway. We found a tendency to increased HIF1α and a significant increase in its regulator, PHD2, in the skeletal muscle after exercise. CONCLUSION: The elderly rats submitted to short-term aerobic physical training did not present skeletal muscle alteration in the protein content of the IL-15 and IL-15-JAK/STAT signaling pathway. However, short-term aerobic physical training was able to modulate the expression of HIF1α and its regulator PHD2, suggesting an essential role of these proteins in improving post-exercise glucose tolerance and insulin sensitivity in elderly rats.


Asunto(s)
Envejecimiento , Glucosa/metabolismo , Interleucina-15/metabolismo , Condicionamiento Físico Animal/fisiología , Transducción de Señal/fisiología , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Prolina Dioxigenasas del Factor Inducible por Hipoxia/metabolismo , Resistencia a la Insulina/fisiología , Músculo Esquelético/metabolismo , Ratas Wistar , Factores de Tiempo
5.
Amino Acids ; 53(9): 1391-1403, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34255136

RESUMEN

Interventions that can modulate subcutaneous white adipose tissue (scWAT) function, such as exercise training and nutritional components, like taurine, modulate the inflammatory process, therefore, may represent strategies for obesity treatment. We investigated the effects of taurine supplementation in conjunction with exercise on inflammatory and oxidative stress markers in plasma and scWAT of obese women. Sixteen obese women were randomized into two groups: Taurine supplementation group (Tau, n = 8) and Taurine supplementation + exercise group (Tau + Exe, n = 8). The intervention was composed of daily taurine supplementation (3 g) and exercise training for 8 weeks. Anthropometry, body fat composition, and markers of inflammatory and oxidative stress were determined in plasma and scWAT biopsy samples before and after the intervention. We found that, although taurine supplementation increased taurine plasma levels, no changes were observed for the anthropometric characteristics. However, Tau alone decreased interleukin-6 (IL-6), and in conjunction with exercise (Tau + Exe), increased anti-inflammatory interleukins (IL-15 and IL10), followed by reduced IL1ß gene expression in the scWAT of obese women. Tau and Tau + Exe groups presented reduced adipocyte size and increased connective tissue and multilocular droplets. In conclusion, taurine supplementation in conjunction with exercise modulated levels of inflammatory markers in plasma and scWAT, and improved scWAT plasticity in obese women, promoting protection against obesity-induced inflammation. TRN NCT04279600 retrospectively registered on August 18, 2019.


Asunto(s)
Tejido Adiposo Blanco/fisiología , Citocinas/sangre , Suplementos Dietéticos , Ejercicio Físico , Obesidad/terapia , Grasa Subcutánea/fisiología , Taurina/administración & dosificación , Tejido Adiposo , Adulto , Biomarcadores/sangre , Composición Corporal , Femenino , Humanos , Persona de Mediana Edad , Obesidad/sangre , Obesidad/patología , Adulto Joven
6.
J Cell Biochem ; 120(4): 5551-5557, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30320909

RESUMEN

The purpose of this study was to investigate the impact of a training season (approximately 7 months) on physiological and salivary immune-endocrine markers in master athletes. Nine male master athletes were evaluated at the beginning of the season (M1) and a week after the main official competition at the end of the sports season (M2). The controlled variables included Maximal oxygen consumption, anthropometric, physiological, and salivary immune-endocrine markers. Master athletes presented a reduced percentage of fat mass and increased lean body mass at the end of the season. VO2max values were similar at M1 and M2, while the maximal heart rate and lactate were lower at M2. No differences were observed in Immunoglobulin A and cortisol levels between moments, whereas testosterone levels and the testosterone/cortisol ratio were significantly lower at the end of the season. The results suggest that maintaining regular training throughout life has positive effects on body composition and improves physiological fitness. However, care should be taken to avoid fatigue as indicated by lower testosterone levels at the end of the season.


Asunto(s)
Atletas , Hidrocortisona , Consumo de Oxígeno/inmunología , Rendimiento Físico Funcional , Saliva , Testosterona , Adulto , Femenino , Humanos , Hidrocortisona/inmunología , Hidrocortisona/metabolismo , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Masculino , Saliva/inmunología , Saliva/metabolismo , Testosterona/inmunología , Testosterona/metabolismo
7.
J Cell Biochem ; 120(1): 697-704, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30206970

RESUMEN

The obesity is a result of energy imbalance and the increase in thermogenesis seems an interesting alternative for the treatment of this disease. The mechanism of energy expenditure through thermogenesis is tightly articulated in the hypothalamus by leptin. The hypothalamic extracellular signal-regulated kinase-1/2 (ERK1/2) is a key mediator of the thermoregulatory effect of leptin and mediates the sympathetic signal to the brown adipose tissue (BAT). In this context, physical exercise is one of the main interventions for the treatment of obesity. Thus, this study aimed to verify the effects of acute physical exercise on leptin-induced hypothalamic ERK1/2 phosphorylation and thermogenesis in obese mice. Here we showed that acute physical exercise reduced the fasting glucose of obese mice and increased leptin-induced hypothalamic p-ERK1/2 and uncoupling protein 1 (UCP1) content in BAT ( P < 0.05). These molecular changes are accompanied by an increased oxygen uptake (VO 2 ) and heat production in obese exercised mice ( P < 0.05). The increased energy expenditure in the obese exercised animals occurred independently of changes in spontaneous activity. Thus, this is the first study demonstrating that acute physical exercise can increase leptin-induced hypothalamic ERK1/2 phosphorylation and energy expenditure of obese mice.


Asunto(s)
Hipotálamo/metabolismo , Leptina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Obesidad/metabolismo , Condicionamiento Físico Animal , Termogénesis/fisiología , Tejido Adiposo Pardo/metabolismo , Animales , Peso Corporal , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético/fisiología , Inyecciones Intraperitoneales , Leptina/administración & dosificación , Ratones , Ratones Obesos , Consumo de Oxígeno/fisiología , Fosforilación/efectos de los fármacos , Proteína Desacopladora 1/metabolismo
8.
Eur J Neurosci ; 50(7): 3181-3190, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31206806

RESUMEN

Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. The APPL1 mediates a positive effect on the insulin signaling through the interaction with the phosphoinositide 3-kinase (PI3K). Thus, the present study aimed to explore the effects of an acute physical exercise session on the hypothalamic adiponectin signaling. Firstly, using bioinformatics analysis, we found a negative correlation between hypothalamic APPL1 mRNA levels and food consumption in several strains of genetically diverse BXD mice. Also, the mice and the human database revealed a positive correlation between the levels of APPL1 mRNA and PI3K mRNA. At the molecular level, the exercised mice showed increased APPL1 and PI3K (p110) protein contents in the hypothalamus of Swiss mice. Furthermore, the exercise increases co-localization between APPL1 and PI3K p110 predominantly in neurons of the arcuate nucleus of hypothalamus (ARC). Finally, we found an acute exercise session reduced the food intake 5 hr after the end of fasting. In conclusion, our results indicate that physical exercise reduces the food intake and increases some proteins related to adiponectin pathway in the hypothalamus of lean mice.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Hipotálamo/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Ingestión de Alimentos/fisiología , Masculino , Ratones , ARN Mensajero/metabolismo , Transducción de Señal
9.
Cytokine ; 115: 1-7, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30616033

RESUMEN

The study aimed to analyze the effects of aging and lifelong training on the main pro- and anti-inflammatory cytokines, and the impact of acute exercise on the expression of these cytokines. Thirty-nine participants were allocated into 3 groups: young (31.8 ±â€¯3.00 yrs.), middle-aged (54.2 ±â€¯5.9 yrs.) and master athletes (53.1 ±â€¯8.8 yrs.) and performed a maximal incremental test on a cycle ergometer. Blood samples were obtained before (Pre), 10 min post-exercise (Post) and 1 h post-exercise (Post 1 h). Mean VO2max was similar for master athletes and youngers and higher compared to the middle-aged group. Resting values of the IL-1ra, IL-1ß, IL-4, and IL-8 were higher in master athletes compared to the young and middle-aged groups (P < 0.01), while the highest values of IL-10 and IL-17 were observed for the youngers (29.49 ±â€¯18.00 pg/mL and 66.24 ±â€¯23.23 pg/mL, respectively) with the middle-aged group showing the lowest values (2.13 ±â€¯1.40 pg/mL). Acute exercise effects (Post) were observed for IL-1ß in the master athletes group, IL-6 in the young group and IL-4 for both groups (P < 0.05). No Post effects were observed for the middle-age group for all cytokines. The TNF-α/IL-10 ratio was higher in all moments for the middle-aged (P < 0.05). In conclusion, lifelong training helps to maintain the balance of pro- and anti-inflammatory cytokines, together with IL-10 levels close to those found in young adults.


Asunto(s)
Citocinas/metabolismo , Ejercicio Físico/fisiología , Inmunosenescencia/fisiología , Adulto , Atletas , Femenino , Humanos , Masculino , Persona de Mediana Edad
10.
Brain Behav Immun ; 79: 284-293, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30797044

RESUMEN

The consumption of saturated fatty acids is one of the leading risk factors for Alzheimer's Disease (AD) development. Indeed, the short-term consumption of a high-fat diet (HFD) is related to increased inflammatory signals in the hippocampus; however, the potential molecular mechanisms linking it to AD pathogenesis are not fully elucidated. In our study, we investigated the effects of short-term HFD feeding (within 3, 7 and 10 days) in AD markers and neuroinflammation in the hippocampus of mice. The short period of HFD increased fasting glucose and HOMA-IR. Also, mice fed HFD increased the protein content of ß-Amyloid, pTau, TNFα, IL1ß, pJNK, PTP1B, peIF2α, CHOP, Caspase3, Cleaved-Caspase3 and Alzheimer-related genes (Bax, PS1, PEN2, Aph1b). At 10 days, both neuronal (N2a) and microglial (BV2) cells presented higher expression of inflammatory and apoptotic genes when stimulated with palmitate. These findings suggest that a short period of consumption of a diet rich in saturated fat is associated with activation of inflammatory, ER stress and apoptotic signals in the hippocampus of young mice.


Asunto(s)
Enfermedad de Alzheimer/etiología , Dieta Alta en Grasa/efectos adversos , Hipocampo/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/metabolismo , Animales , Apoptosis , Modelos Animales de Enfermedad , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/fisiología , Inflamación/metabolismo , Interleucina-1beta , Ratones , Ratones Transgénicos , Microglía/metabolismo , Neuronas/metabolismo , Fosforilación , Transducción de Señal/efectos de los fármacos , Lóbulo Temporal/metabolismo , Proteínas tau/metabolismo
11.
Cytokine ; 110: 87-93, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29705396

RESUMEN

Adiponectin is considered an adipokine that has essential anti-inflammatory and insulin-sensitivity actions. The adaptor protein containing the pleckstrin homology domain, the phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a protein involved in adiponectin signaling that plays a role in many physiological and pathophysiological processes. In the central nervous system, adiponectin can potentiate the effects of leptin in the arcuate proopiomelanocortin (POMC) neurons. However, the role of APPL1 in the hypothalamus is not well understood. Therefore, in this study, we explored the effects of acute physical exercise on APPL1 protein content in the hypothalamus and food intake control in leptin stimulated-obese mice. Here we show that acute exercise increased serum adiponectin levels and APPL1 content in the hypothalamus, which were followed by reduced food intake in obese mice. Further, at the molecular level, the exercised obese mice increased the protein kinase B (Akt) signaling in the hypothalamus and attenuated the mammalian homolog of Drosophila tribbles protein 3 (TRB3) levels. In conclusion, the results indicate physical exercise is capable of increasing APPL1 protein content in the hypothalamus of leptin stimulated-obese mice and modulating food intake.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Hipotálamo/metabolismo , Condicionamiento Físico Animal/fisiología , Adiponectina/metabolismo , Animales , Proteínas de Ciclo Celular/metabolismo , Ingestión de Alimentos/fisiología , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Leptina/metabolismo , Ratones , Ratones Obesos , Neuronas/metabolismo , Neuronas/fisiología , Obesidad/metabolismo , Obesidad/fisiopatología , Fosforilación/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología
12.
Drug Dev Res ; 78(5): 203-209, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28718949

RESUMEN

Preclinical Research Metabolic disorders are responsible for more than 60% of all deaths worldwide. Calcitriol or vitamin D (vitD) deficiency is associated with a large proportion of these diseases is an important therapeutic target for exploration. This study evaluated the administration of high doses of vitD (3000 IU/kg) in obese and insulin-resistant C57BL/6J mice. Our results demonstrated that although high doses of vitD provided metabolic benefits such as increased insulin sensitivity and decreased body mass, this was associated with significant damage in the kidneys of obese mice. These findings support the role of vitD as a therapeutic strategy against metabolic disorders. However, caution is required with the dose administrated, and the renal damage associated still needs to be investigated. Drug Dev Res 78 : 203-209, 2017. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Metabolismo Energético/efectos de los fármacos , Obesidad/tratamiento farmacológico , Vitamina D/administración & dosificación , Animales , Índice de Masa Corporal , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Relación Dosis-Respuesta a Droga , Resistencia a la Insulina , Masculino , Ratones , Vitamina D/efectos adversos
14.
Artículo en Inglés | MEDLINE | ID: mdl-38197701

RESUMEN

White adipose tissue (WAT) controls energy storage, expenditure, and endocrine function. Rho-kinase (ROCK) is related to impaired thermogenesis, downregulation of preadipocyte differentiation, and adipokine production. Furthermore, WAT ROCK responds to metabolic stress from high-fat diets or diabetes. However, ROCK distribution in adipose depots and its response to aging and sex remain unclear. Thus, we aim to investigate ROCK function in adipose tissue of rodent and human in response to aging and sex. We observed specific differences in the ROCK1/2 distribution in inguinal WAT (ingWAT), perigonadal WAT (pgWAT), and brown adipose tissue of male and female rodents. However, ROCK2 expression was lower in female ingWAT compared with males, a fact that was not observed in the other depots. In the pgWAT and ingWAT of male and female rodents, ROCK activity increased during development. Moreover, middle-aged female rodents and humans showed downregulation in ROCK activity after acute physical exercise. Interestingly, ROCK levels were associated with several inflammatory markers both in rats and humans WAT (Nfkb1, Tnf, Il1b, Il6, and Mcp1). Induction of cell senescence by etoposide elevates ROCK activity in human preadipocytes; however, silencing ROCK1/2 demonstrates improvement in the inflammatory and cell senescence state. Using public databases, several pathways were strongly associated with ROCK modulation in WAT. In summary, WAT ROCK increases with development in association with inflammatory markers. Further, ROCK activity was attenuated by acute physical exercise, implicating it as a possible therapeutic target for metabolism improvement mediated by adipose tissue inflammatory state changes.


Asunto(s)
Roedores , Quinasas Asociadas a rho , Humanos , Ratas , Masculino , Femenino , Animales , Persona de Mediana Edad , Quinasas Asociadas a rho/fisiología , Obesidad/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Envejecimiento , Tejido Adiposo
15.
Ageing Res Rev ; 87: 101935, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37062444

RESUMEN

Physical training is a potent therapeutic approach for improving mitochondrial health through peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) signaling pathways. However, comprehensive information regarding the physical training impact on PGC-1α in the different physiological systems with advancing age is not fully understood. This review sheds light on the frontier-of-knowledge data regarding the chronic effects of exercise on the PGC-1α signaling pathways in rodents and humans. We address the molecular mechanisms involved in the different tissues, clarifying the precise biological action of PGC-1α, restricted to the aged cell type. Distinct exercise protocols (short and long-term) and modalities (aerobic and resistance exercise) increase the transcriptional and translational PGC-1α levels in adipose tissue, brain, heart, liver, and skeletal muscle in animal models, suggesting that this versatile molecule induces pleiotropic responses. However, PGC-1α function in some human tissues (adipose tissue, heart, and brain) remains challenging for further investigations. PGC-1α is not a simple transcriptional coactivator but supports a biochemical environment of mitochondrial dynamics, controlling physiological processes (primary metabolism, tissue remodeling, autophagy, inflammation, and redox balance). Acting as an adaptive mechanism, the long-term effects of PGC-1α following exercise may reflect the energy demand to coordinate multiple organs and contribute to cellular longevity.


Asunto(s)
Condicionamiento Físico Animal , Fenómenos Fisiológicos , Animales , Humanos , Anciano , Ejercicio Físico , Factores de Transcripción/metabolismo , Músculo Esquelético/fisiología , Envejecimiento/fisiología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Condicionamiento Físico Animal/fisiología
16.
J Nutr Biochem ; 114: 109270, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36706930

RESUMEN

It is known that long-term high-fat diet (HF) feeding drastically affects the adipose tissue, contributing to metabolic disorders. Recently, short-term HF consumption was shown to affect different neuronal signaling pathways. Thus, we aimed to evaluate the inflammatory effects of a short-term HF and whether a diet containing omega-3 fatty acid fats from flaxseed oil (FS) has protective effects. Mice were divided into three groups for 3 d, according to their diets: Control group (CT), HF, or FS for 3 d. Lipid profiles were assessed through mass spectrometry and inflammatory markers by RT-qPCR and Western blotting. After short-term HF, mice increased food intake, body weight, adiposity, and fasting glucose. Increased mRNA content of Ccl2 and Tnf was demonstrated in the HF compared to CT in mesenteric adipose tissue. In the liver, TNFα protein was higher in the HF group than in CT, followed by a decreased polyunsaturated fatty acids tissue incorporation in HF. On the other hand, the consumption of FS reduced food intake and fasting glucose, as well as increased omega-3 fatty acid incorporation in MAT and the liver. However, short-term FS was insufficient to control the early inflammation triggered by HF in MAT and the liver. These data demonstrated that a 3-d HF diet is enough to damage glucose homeostasis and trigger inflammation. In contrast, short-term FS protects against increased food intake and fasting glucose but not inflammation in mice.


Asunto(s)
Dieta Alta en Grasa , Ácidos Grasos Omega-3 , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Aceite de Linaza/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/metabolismo , Inflamación/metabolismo , Tejido Adiposo/metabolismo , Glucosa/metabolismo , Ratones Endogámicos C57BL
17.
Life Sci ; 290: 120229, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34914931

RESUMEN

Lipokines are bioactive compounds, derived from adipose tissue depots, that control several molecular signaling pathways. Recently, 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), an oxylipin, has gained prominence in the scientific literature. An increase in circulating 12,13-diHOME has been associated with improved metabolic health, and the action of this molecule appears to be mediated by brown adipose tissue (BAT). Scientific evidence indicates that the increase in serum levels of 12,13-diHOME caused by stimuli such as physical exercise and exposure to cold may favor the absorption of fatty acids by brown adipose tissue and stimulate the browning process in white adipose tissue (WAT). Thus, strategies capable of increasing 12,13-diHOME levels may be promising for the prevention and treatment of obesity and metabolic diseases. This review explores the relationship of 12,13-diHOME with brown adipose tissue and its role in the metabolic health context, as well as the signaling pathways involved between 12,13-diHOME and BAT.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/metabolismo , Ácidos Oléicos/metabolismo , Tejido Adiposo Blanco/metabolismo , Humanos , Terapia Molecular Dirigida , Ácidos Oléicos/sangre , Ácidos Oléicos/farmacología , Oxilipinas/metabolismo
18.
Mech Ageing Dev ; 200: 111598, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34762939

RESUMEN

Aging is characterized by several physiological changes in the human body, such as the remodeling/redistribution of body fat, highlighted by the increase in fat in the abdominal region due to reduced fat in the peripheral limbs. Abdominal fat is related to metabolic complications and an increased risk for developing diseases such as obesity, type 2 diabetes mellitus, and hypertension. Understanding this process is crucial for developing new therapeutic strategies able to mitigate its impact. This redistribution of fat has been associated with lower activation of brown adipose tissue over the years of life. Brown adipose tissue differs from white adipose tissue, mainly because it produces heat, increasing energy expenditure. Current evidence points to morphological and functional changes in mitochondria during aging, a key mechanism for understanding the dysmetabolic and pro-inflammatory phenotype associated with senescence. Therefore, this minireview will focus on how aging-induced mitochondrial changes are involved in the remodeling/redistribution of body fat.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Envejecimiento , Metabolismo Energético/fisiología , Mitocondrias/metabolismo , Envejecimiento/metabolismo , Envejecimiento/patología , Distribución de la Grasa Corporal , Humanos
19.
Trials ; 22(1): 927, 2021 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-34922604

RESUMEN

The low-grade inflammation is pivotal in obesity and its comorbidities; however, the inflammatory proteins are out of target for traditional drug therapy. Omega-3 (ω3) fatty acids can modulate the downstream signaling of Toll-like receptor (TLR) and tumor necrosis factor-α receptor (TNFα) through GPR120, a G-protein-coupled receptor, a mechanism not yet elucidated in humans. This work aims to investigate if the ω3 supplementation, at a feasible level below the previously recommended level in the literature, is enough to disrupt the inflammation and endoplasmic reticulum stress (ER-stress), and also if in acute treatment (3 h) ω3 can activate the GPR120 in peripheral blood mononuclear cells (PBMC) and leukocytes from overweight non-alcoholic fatty liver disease (NAFLD) participants. The R270H variant of the Ffar4 (GPR120 gene) will also be explored about molecular responses and blood lipid profiles. A triple-blind, prospective clinical trial will be conducted in overweight men and women, aged 19-75 years, randomized into placebo or supplemented (2.2 g of ω3 [EPA+DHA]) groups for 28 days. For sample calculation, it was considered the variation of TNFα protein and a 40% dropout rate, obtaining 22 individuals in each group. Volunteers will be recruited among patients with NAFLD diagnosis. Anthropometric parameters, food intake, physical activity, total serum lipids, complete fatty acid blood profile, and glycemia will be evaluated pre- and post-supplementation. In the PBMC and neutrophils, the protein content and gene expression of markers related to inflammation (TNFα, MCP1, IL1ß, IL6, IL10, JNK, and TAK1), ER-stress (ATF1, ATF6, IRE1, XBP1, CHOP, eIF2α, eIF4, HSP), and ω3 pathway (GPR120, ß-arrestin2, Tab1/2, and TAK1) will be evaluated using Western blot and RT-qPCR. Participants will be genotyped for the R270H (rs116454156) variant using the TaqMan assay. It is hypothesized that attenuation of inflammation and ER-stress signaling pathways in overweight and NAFLD participants will be achieved through ω3 supplementation through binding to the GPR120 receptor. TRIAL REGISTRATION: ClinicalTrials.gov #RBR-7x8tbx. Registered on May 10, 2018, with the Brazilian Registry of Clinical Trials.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Estrés del Retículo Endoplásmico , Humanos , Inflamación , Leucocitos Mononucleares , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Sobrepeso , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
Clin Nutr ; 40(4): 2180-2187, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33051044

RESUMEN

PURPOSE: To evaluate the effects of taurine supplementation associated or not with chronic exercise on body composition, mitochondrial function, and expression of genes related to mitochondrial activity and lipid oxidation in the subcutaneous white adipose tissue (scWAT) of obese women. METHODS: A randomized and double-blind trial was developed with 24 obese women (BMI 33.1 ± 2.9 kg/m2, 32.9 ± 6.3 y) randomized into three groups: Taurine supplementation group (Tau, n = 8); Exercise group (Ex, n = 8); Taurine supplementation + exercise group (TauEx, n = 8). The intervention was composed of 3 g of taurine or placebo supplementation and exercise training for eight weeks. Anthropometry, body fat composition, indirect calorimetry, scWAT biopsy for mitochondrial respiration, and gene expression related to mitochondrial activity and lipid oxidation were assessed before and after the intervention. RESULTS: No changes were observed for the anthropometric characteristics. The Ex group presented an increased resting energy expenditure rate, and the TauEx and Ex groups presented increased lipid oxidation and a decreased respiratory quotient. Both trained groups (TauEx and Ex) demonstrated improved scWAT mitochondrial respiratory capacity. Regarding mitochondrial markers, no changes were observed for the Tau group. The TauEx group had higher expression of CIDEA, PGC1a, PRDM16, UCP1, and UCP2. The genes related to fat oxidation (ACO2 and ACOX1) were increased in the Tau and Ex groups, while only the TauEx group presented increased expression of CPT1, PPARa, PPARγ, LPL, ACO1, ACO2, HSL, ACOX1, and CD36 genes. CONCLUSION: Taurine supplementation associated with exercise improved lipid metabolism through the modulation of genes related to mitochondrial activity and fatty acid oxidation, suggesting a browning effect in the scWAT of obese women.


Asunto(s)
Tejido Adiposo Blanco/metabolismo , Ejercicio Físico , Ácidos Grasos/metabolismo , Mitocondrias/metabolismo , Obesidad/metabolismo , Taurina/administración & dosificación , Adulto , Composición Corporal/efectos de los fármacos , Suplementos Dietéticos , Método Doble Ciego , Metabolismo Energético/efectos de los fármacos , Femenino , Expresión Génica , Humanos , Peroxidación de Lípido/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Oxidación-Reducción/efectos de los fármacos , Placebos , Grasa Subcutánea
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