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1.
Adipocyte ; 13(1): 2339418, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38706095

RESUMEN

A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO). While young, regular chow diet-fed aKO mice showed increased insulin sensitivity, following prolonged (33 weeks) high-fat diet (HFD) exposure, aKO mice developed obesity and insulin resistance. Compared to controls, aKO mice showed less inflammatory adipokine profile despite the significant increase in adiposity. In brown adipose tissue, aKO mice on HFD had changes in CD8+ T cell populations indicating a lesser inflammatory pattern. Following HFD, both aKO and control littermates demonstrated decreased adipose tissue pro-inflammatory macrophages, and increased anti-inflammatory accumulation, without differences between the genotypes. Collectively, our observations indicate that selective deletion of ADAM10 in adipocytes results in a mitigated inflammatory response, leading to increased insulin sensitivity in young mice fed with regular diet. This state of insulin sensitivity, following prolonged HFD, facilitates energy storage resulting in increased fat accumulation which ultimately leads to the development of a phenotype of obesity and insulin resistance. In conclusion, the data indicate that ADAM10 has a modulatory effect of inflammation and whole-body energy metabolism.


Asunto(s)
Proteína ADAM10 , Tejido Adiposo , Dieta Alta en Grasa , Ratones Noqueados , Animales , Masculino , Ratones , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Dieta Alta en Grasa/efectos adversos , Inflamación/metabolismo , Resistencia a la Insulina , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Obesidad/metabolismo , Obesidad/etiología , Fenotipo
2.
Physiol Res ; 73(2): 273-284, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38710057

RESUMEN

Lifestyle intervention encompassing nutrition and physical activity are effective strategies to prevent progressive lipid deposition in the liver. This study aimed to explore the effect of dietary change, and/or high-intensity interval training (HIIT) on hepatic lipid accumulation in high fat diet (HFD)-induced obese rats. We divided lean rats into lean control (LC) or HIIT groups (LH), and obese rats into obese normal chow diet (ND) control (ONC) or HIIT groups (ONH) and obese HFD control (OHC) or HIIT groups (OHH). We found that dietary or HIIT intervention significantly decreased body weight and the risk of dyslipidemia, prevented hepatic lipid accumulation. HIIT significantly improved mitochondrial fatty acid oxidation through upregulating mitochondrial enzyme activities, mitochondrial function and AMPK/PPARalpha/CPT1alpha pathway, as well as inhibiting hepatic de novo lipogenesis in obese HFD rats. These findings indicate that dietary alone or HIIT intervention powerfully improve intrahepatic storage of fat in diet induced obese rats. Keywords: Obesity, Exercise, Diet, Mitochondrial function, Lipid deposition.


Asunto(s)
Dieta Alta en Grasa , Entrenamiento de Intervalos de Alta Intensidad , Metabolismo de los Lípidos , Hígado , Obesidad , Ratas Sprague-Dawley , Animales , Obesidad/metabolismo , Obesidad/terapia , Masculino , Dieta Alta en Grasa/efectos adversos , Ratas , Hígado/metabolismo , Condicionamiento Físico Animal/fisiología
5.
Chron Respir Dis ; 21: 14799731241251827, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38717428

RESUMEN

Asthma and obstructive sleep apnea (OSA) are common respiratory disorders. They share characteristics such as airway obstruction, poor sleep quality, and low quality of life. They are often present as comorbidities, along with obesity, gastroesophageal reflux disease (GERD), and allergic rhinitis (AR), which impacts the disease's control. In recent years, there has been discussion about the association between these conditions and their pathophysiological and clinical consequences, resulting in worse health outcomes, increased healthcare resource consumption, prolonged hospital stays, and increased morbidity and mortality. Some studies demonstrate that treatment with continuous positive airway pressure (CPAP) can have a beneficial effect on both pathologies. This review summarizes the existing evidence of the association between asthma and OSA at their pathophysiological, epidemiological, clinical, and therapeutic levels. It intends to raise awareness among healthcare professionals about these conditions and the need for further research.


Asunto(s)
Asma , Presión de las Vías Aéreas Positiva Contínua , Reflujo Gastroesofágico , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/epidemiología , Asma/terapia , Asma/epidemiología , Asma/complicaciones , Presión de las Vías Aéreas Positiva Contínua/métodos , Reflujo Gastroesofágico/terapia , Reflujo Gastroesofágico/epidemiología , Rinitis Alérgica/terapia , Rinitis Alérgica/complicaciones , Rinitis Alérgica/epidemiología , Comorbilidad , Obesidad/complicaciones , Obesidad/terapia , Obesidad/epidemiología , Calidad de Vida , Atención Integral de Salud/métodos
6.
Sci Rep ; 14(1): 10541, 2024 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719835

RESUMEN

To examine the joint association of electronic screen time (EST), moderate-to-vigorous physical activity time (MVPA) and overweight/obesity with early pubertal development (EPD) in girls. A case-control study of 177 EPD girls and 354 girls with normal pubertal development was conducted between October 2019 and August 2022. Overweight/obesity was defined as body mass index ≥ 85th percentiles for age and sex. We found a non-significant increase of EPD risk among girls with high EST alone [OR: 2.75 (0.65-11.58)] or low MVPA alone [OR: 2.54 (0.74-8.69)], but a significant increase of EPD risk among girls with overweight/obesity alone [OR: 4.91 (1.01-23.92)], compared to girls without any of the three risk factors (low MVPA, high EST and overweight/obesity). Girls with any two of the three risk factors faced increased risk of EPD, and girls with all three risk factors faced the highest risk of EPD [OR and 95% CI: 26.10 (6.40-106.45)]. Being overweight/obesity might be more important than having low MVPA or high EST as a correlate of EPD compared to girls without any of the three risk factors, but the co-presence of low MVPA, high EST and overweight/obesity would largely increase the risk of EPD in girls.


Asunto(s)
Ejercicio Físico , Pubertad , Tiempo de Pantalla , Humanos , Femenino , Estudios de Casos y Controles , Niño , Pubertad/fisiología , Factores de Riesgo , Índice de Masa Corporal , Sobrepeso , Adolescente , Obesidad Infantil/epidemiología , Obesidad/epidemiología
7.
Sci Rep ; 14(1): 10557, 2024 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719889

RESUMEN

Cardiometabolic multimorbidity (CM), defined as the coexistence of two or three cardiometabolic disorders, is one of the most common and deleterious multimorbidities. This study aimed to investigate the association of Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with the prevalence of CM. The data were obtained from the 2021 health checkup database for residents of the Electronic Health Management Center in Xinzheng, Henan Province, China. 81,532 participants aged ≥ 60 years were included in this study. Logistic regression models were used to estimate the odd ratios (ORs) and 95% confidence intervals (CIs) for CUN-BAE, BMI, WC, and WHtR in CM. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory ability of different anthropometric indicators for CM. The multivariable-adjusted ORs (95% CIs) (per 1 SD increase) of CM were 1.799 (1.710-1.893) for CUN-BAE, 1.329 (1.295-1.364) for BMI, 1.343 (1.308-1.378) for WC, and 1.314 (1.280-1.349) for WHtR, respectively. Compared with BMI, WC and WHtR, CUN-BAE had the highest AUC in both males and females (AUC: 0.642; 95% CI 0.630-0.653 for males, AUC: 0.614; 95% CI 0.630-0.653 for females). CUN-BAE may be a better measure of the adverse effect of adiposity on the prevalence of CM than BMI, WC, and WHtR.


Asunto(s)
Adiposidad , Índice de Masa Corporal , Multimorbilidad , Obesidad , Circunferencia de la Cintura , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Obesidad/epidemiología , Anciano , China/epidemiología , Relación Cintura-Estatura , Prevalencia , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Curva ROC
8.
BMC Public Health ; 24(1): 1273, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724957

RESUMEN

OBJECTIVE: This study aims to investigate the relationship between obesity and constipation among American adults. METHODS: Our study leveraged data from the National Health and Nutrition Examination Survey (NHANES). This comprehensive approach enabled us to summarize the weighted prevalence rates of obesity in adults. To further deepen our understanding, we employed a variety of analytical methods. These included multivariable logistic regression, subgroup analysis and restricted cubic splines. Through these methodologies, we were able to effectively evaluate the correlation between various obesity indicators and constipation, offering new insights into this complex relationship. RESULTS: The weighted prevalence of constipation stands at 9.42%. Notably, an increased risk of constipation is linked with a BMI (body mass index) exceeding 28 kg/m2, WSR (waist-stature ratio) that is either between 58.3 and 64.8 or above 64.8, as well as a LAP (lipid accumulation products) ranging from 50.8 to 90.1. In contrast, a reduced risk of constipation is associated with WWI (weight-adjusted-waist index) that falls between 0.015 and 0.020, exceeds 0.020, and without the presence of central obesity (P < 0.05). Restricted cubic spline analysis, a significant non-linear relationship was discerned between BMI, WSR, and LAP in relation to constipation. CONCLUSIONS: This pioneering large-scale study explores the relationship between various obesity indices and constipation. It reveals that reducing the BMI, WSR, LAP and waist circumference can decrease the risk of constipation. Conversely, a higher value of WWI correlates with a lower constipation risk, and this remains true even after adjusting for a wide range of variables.


Asunto(s)
Índice de Masa Corporal , Estreñimiento , Encuestas Nutricionales , Obesidad , Humanos , Estreñimiento/epidemiología , Obesidad/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Prevalencia , Factores de Riesgo , Anciano , Adulto Joven
9.
Int J Epidemiol ; 53(3)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38725300

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC. METHODS: We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR-Egger, Contamination Mixture). We used multivariable MR for the mediation analyses. RESULTS: Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95% CI: 1.08-1.24, P-value = 1.4 × 10-5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2-13%) of the association], smoking (31%, 4-57%) and PA (7%, 2-11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA. CONCLUSIONS: The effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI-CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation.


Asunto(s)
Índice de Masa Corporal , Neoplasias Colorrectales , Análisis de la Aleatorización Mendeliana , Obesidad , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/epidemiología , Factores de Riesgo , Obesidad/genética , Obesidad/epidemiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Consumo de Bebidas Alcohólicas/epidemiología
10.
Cells ; 13(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38727299

RESUMEN

The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy surplus, the subcutaneous white adipose tissue (WAT) is capable of expanding through the enlargement of existing adipocytes (hypertrophy), followed by de novo adipogenesis (hyperplasia), which is impaired in hypertrophic obesity. However, an impaired hyperplastic response may result from various defects in adipogenesis, leading to different WAT features and metabolic consequences, as discussed here by reviewing the results of the studies in animal models with either overexpression or knockdown of the main molecular regulators of the two steps of the adipogenesis process. Moreover, impaired WAT remodeling with aging has been associated with various age-related conditions and reduced lifespan expectancy. Here, we delve into the latest advancements in comprehending the molecular and cellular processes underlying age-related changes in WAT function, their involvement in common aging pathologies, and their potential as therapeutic targets to influence both the health of elderly people and longevity. Overall, this review aims to encourage research on the mechanisms of WAT maladaptation common to conditions of both excessive and insufficient fat tissue. The goal is to devise adipocyte-targeted therapies that are effective against both obesity- and age-related disorders.


Asunto(s)
Adipogénesis , Tejido Adiposo Blanco , Envejecimiento , Obesidad , Humanos , Envejecimiento/patología , Obesidad/patología , Obesidad/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Adipocitos/metabolismo , Adipocitos/patología
11.
Medicine (Baltimore) ; 103(19): e38141, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728452

RESUMEN

Obesity rates continue to rise globally, posing a significant public health concern. Current treatments often lack long-term effectiveness, necessitating the exploration of new approaches. This study examines the effectiveness of a modified treatment method called Cognitive Behavioral Therapy modified as FIRE method (CBT-F), which combines cognitive behavioral therapy with pharmacotherapy. The study involves 62 women seeking weight loss treatment, divided into a CBT-F group and a control group receiving only pharmacotherapy. Anthropometric measures and blood chemistry data were collected over an average follow-up period of 68.5 days. The results demonstrate that the CBT-F group achieved significantly greater weight loss compared to the control group. No notable differences were observed in blood chemistry data. The combination of CBT-F and pharmacotherapy offers a comprehensive and planned approach to obesity treatment by addressing psychological factors and leveraging the effects of medication. Modules specifically designed to handle medication side effects and changes in eating behavior may contribute to treatment success and sustainability. Although this study focused on women, future research should examine the effectiveness of CBT-F in diverse populations. CBT-F shows promise as an alternative or complementary treatment option for individuals who have undergone CBT for extended periods or struggle with lifestyle changes. Overall, the findings suggest that CBT-F, with its shorter treatment duration and immediate effects of pharmacotherapy, holds potential as an effective and sustainable approach to obesity treatment. Further studies are necessary to validate these findings and expand the evidence base for this novel treatment.


Asunto(s)
Terapia Cognitivo-Conductual , Obesidad , Pérdida de Peso , Humanos , Terapia Cognitivo-Conductual/métodos , Femenino , Obesidad/terapia , Pérdida de Peso/efectos de los fármacos , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Terapia Combinada , Fármacos Antiobesidad/uso terapéutico , Resultado del Tratamiento
12.
Artif Cells Nanomed Biotechnol ; 52(1): 278-290, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38733373

RESUMEN

Type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), obesity (OB) and hypertension (HT) are categorized as metabolic disorders (MDs), which develop independently without distinct borders. Herein, we examined the gut microbiota (GM) and Saururus chinensis (SC) to confirm their therapeutic effects via integrated pharmacology. The overlapping targets from the four diseases were determined to be key protein coding genes. The protein-protein interaction (PPI) networks, and the SC, GM, signalling pathway, target and metabolite (SGSTM) networks were analysed via RPackage. Additionally, molecular docking tests (MDTs) and density functional theory (DFT) analysis were conducted to determine the affinity and stability of the conformer(s). TNF was the main target in the PPI analysis, and equol derived from Lactobacillus paracasei JS1 was the most effective agent for the formation of the TNF complex. The SC agonism (PPAR signalling pathway), and antagonism (neurotrophin signalling pathway) by SC were identified as agonistic bioactives (aromadendrane, stigmasta-5,22-dien-3-ol, 3,6,6-trimethyl-3,4,5,7,8,9-hexahydro-1H-2-benzoxepine, 4α-5α-epoxycholestane and kinic acid), and antagonistic bioactives (STK734327 and piclamilast), respectively, via MDT. Finally, STK734327-MAPK1 was the most favourable conformer according to DFT. Overall, the seven bioactives from SC and equol that can be produced by Lactobacillus paracasei JS1 can exert synergistic effects on these four diseases.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hipertensión , Enfermedad del Hígado Graso no Alcohólico , Obesidad , Saururaceae , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/microbiología , Obesidad/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertensión/microbiología , Hipertensión/metabolismo , Hipertensión/tratamiento farmacológico , Animales , Saururaceae/química , Saururaceae/metabolismo , Simulación del Acoplamiento Molecular , Humanos , Mapas de Interacción de Proteínas
13.
Rev Assoc Med Bras (1992) ; 70(4): e20231214, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716942

RESUMEN

OBJECTIVE: Obesity is a chronic multisystem disease associated with increased morbidity and mortality. Obesity, which is a complex, multifactorial, and heterogeneous condition, is thought to result from the interaction of environmental, physiological, and genetic factors. In this study, the relationship between serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB in obese and healthy cohorts was evaluated along with biochemical and gene expressions and with demographic and clinical covariates, and their effects on obesity were evaluated. METHODS: This case-control study included a total of 80 individuals, 40 healthy controls and 40 obesity patients, consisting of female and male aged between 18 and 63 years. Hemoglobin A1c, mucin-1, and nuclear factor κB levels were determined by ELISA in serum samples obtained from patients. In addition, aspartate aminotransferase, alanine transaminase, low density lipoprotein, and glucose values were measured. The gene expressions of the same markers were analyzed by quantitative real-time polymerase chain reaction, and their regulation status was defined. RESULTS: Serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB were found to be high in obese individuals (p<0.05). The gene expression of these serum markers was found to be upregulated. Of the anthropometric measurements, waist circumference and body mass index were correlated with both serum markers and gene expressions (p<0.05). CONCLUSION: In addition to the known association of hemoglobin A1c and nuclear factor κB with obesity, serum levels of mucin-1 as well as upregulation of genes point to its modifier effect on obesity. These parameters can be the powerful markers in the diagnosis of obesity.


Asunto(s)
Biomarcadores , Índice de Masa Corporal , Hemoglobina Glucada , Mucina-1 , FN-kappa B , Obesidad , Humanos , Masculino , Obesidad/sangre , Femenino , Hemoglobina Glucada/análisis , Adulto , FN-kappa B/sangre , Estudios de Casos y Controles , Persona de Mediana Edad , Adulto Joven , Mucina-1/sangre , Adolescente , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Reacción en Cadena en Tiempo Real de la Polimerasa
14.
Eat Weight Disord ; 29(1): 35, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717596

RESUMEN

PURPOSE: ACTION Teens (NCT05013359) was conducted in 10 countries to identify perceptions, attitudes, behaviors, and barriers to effective obesity care among adolescents living with obesity (ALwO), caregivers of ALwO, and healthcare professionals (HCPs). Here, we report data from participants in Italy. METHODS: The ACTION Teens cross-sectional online survey was completed by 649 ALwO (aged 12- < 18 years), 455 caregivers, and 252 HCPs in Italy in 2021. RESULTS: Most ALwO thought their weight was above normal (69%), worried about weight affecting their future health (87%), and reported making a weight-loss attempt in the past year (60%); fewer caregivers responded similarly regarding their child (46%, 72%, and 33%, respectively). In addition, 49% of caregivers believed their child would lose excess weight with age. ALwO (38%) and caregivers (30%) most often selected wanting to be more fit/in better shape as a weight-loss motivator for ALwO; HCPs most often selected improved social life/popularity (73%). ALwO (25%) and caregivers (22%) most frequently selected lack of hunger control and not liking exercise, respectively, as weight-loss barriers, while HCPs most often agreed that unhealthy eating habits were a barrier (93%). ALwO most often obtained weight-management information from family/friends (25%) and search engines (24%); caregivers most often obtained information from doctors (29%). CONCLUSION: In Italy, the impact of obesity on ALwO was underestimated by caregivers, and ALwO and HCPs had different perceptions of key weight-loss motivators and barriers. Additionally, the internet was a key information source for ALwO, which suggests new education/communication strategies are needed. LEVEL OF EVIDENCE: IV; Evidence obtained from multiple time series with/without intervention, e.g. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05013359.


Asunto(s)
Cuidadores , Personal de Salud , Humanos , Italia , Adolescente , Femenino , Masculino , Cuidadores/psicología , Personal de Salud/psicología , Estudios Transversales , Niño , Conocimientos, Actitudes y Práctica en Salud , Obesidad Infantil/psicología , Obesidad Infantil/terapia , Adulto , Encuestas y Cuestionarios , Obesidad/psicología , Obesidad/terapia , Conducta del Adolescente/psicología
15.
Nat Commun ; 15(1): 3982, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729945

RESUMEN

The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.


Asunto(s)
Retículo Endoplásmico , Ayuno , Hepatocitos , Hígado , Obesidad , Ayuno/metabolismo , Retículo Endoplásmico/metabolismo , Animales , Hepatocitos/metabolismo , Obesidad/metabolismo , Obesidad/patología , Hígado/metabolismo , Ratones , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/ultraestructura , Ácidos Grasos/metabolismo , Humanos , Oxidación-Reducción , Proteínas Ribosómicas/metabolismo
16.
Respir Res ; 25(1): 205, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730297

RESUMEN

BACKGROUND: Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear. METHODS: mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs. RESULTS: Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate. CONCLUSION: Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.


Asunto(s)
Carboxiliasas , Células Endoteliales , Pulmón , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2 , Obesidad , Succinatos , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Ratones , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/patología , Carboxiliasas/metabolismo , Carboxiliasas/genética , Obesidad/metabolismo , Obesidad/complicaciones , Masculino , Succinatos/farmacología , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/irrigación sanguínea , Células Cultivadas , Microvasos/metabolismo , Microvasos/efectos de los fármacos , Microvasos/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Dieta Alta en Grasa/efectos adversos , Endotelio Vascular/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Hidroliasas
17.
BMC Psychiatry ; 24(1): 351, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730360

RESUMEN

BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.


Asunto(s)
Depresión , Obesidad , Humanos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Obesidad/epidemiología , Depresión/epidemiología , Depresión/sangre , Anciano , Estudios Longitudinales , Factores de Riesgo , Índice de Masa Corporal , Lípidos/sangre , Circunferencia de la Cintura , Pueblos del Este de Asia
18.
BMC Med Genomics ; 17(1): 128, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730451

RESUMEN

The parallel rise in obesity and male infertility in modern societies necessitates the identification of susceptibility genes underlying these interconnected health issues. In our study, we conducted a comprehensive search in the OMIM database to identify genes commonly associated with male infertility and obesity. Subsequently, we performed an insilico analysis using the REVEL algorithm to detect pathogenic single nucleotide polymorphisms (SNPs) in the coding region of these candidate genes. To validate our findings in vivo, we conducted a comprehensive analysis of SNPs and gene expression of candidate genes in 200 obese infertile subjects and 240 obese fertile individuals using ARMS-PCR. Additionally, we analyzed 20 fertile and 22 infertile obese individuals using Realtime-qPCR. By removing duplicated queries, we obtained 197 obesity-related genes and 102 male infertility-related genes from the OMIM database. Interestingly, the APOB gene was found in common between the two datasets. REVEL identified the rs13306194 variant as potentially pathogenic with a calculated score of 0.524. The study identified a significant association between the AA (P value = 0.001) genotype and A allele (P value = 0.003) of the APOB rs13306194 variant and infertility in obese men. APOB expression levels were significantly lower in obese infertile men compared to obese fertile controls (p < 0.01). Moreover, the AA genotype of rs13306194 APOB was associated with a significant decrease in APOB gene expression in obese infertile men (p = 0.05). There is a significant association between the Waist-to-Hip Ratio (WHR) and LH with infertility in the obese infertile group. These results are likely to contribute to a better understanding of the causes of male infertility and its association with obesity.


Asunto(s)
Infertilidad Masculina , Obesidad , Polimorfismo de Nucleótido Simple , Humanos , Masculino , Infertilidad Masculina/genética , Obesidad/genética , Obesidad/complicaciones , Adulto , Predisposición Genética a la Enfermedad , Estudios de Casos y Controles
19.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38731797

RESUMEN

Adipocyte P2 (aP2), also known as FABP4, is an adipokine that adipose tissue produces and expresses in macrophages. Its primary role is to facilitate the transportation of fatty acids across cell membranes. Numerous studies have reported associations between FABP4 and the development of metabolic disorders. However, there is limited knowledge regarding FABP4 expression in diabetes and obesity, especially about different age groups, genders, and ethnicities. This study aims to investigate the association between FABP4 levels, diabetes mellitus, and obesity within various ethnic groups. We measured plasma FABP4 concentrations in a cohort of 2083 patients from the KDEP study and gathered anthropometric data. Additionally, we collected and analyzed clinical, biochemical, and glycemic markers using multivariate regression analysis. The average FABP4 concentration was significantly higher in female participants than in males (18.8 ng/mL vs. 14.4 ng/mL, p < 0.001, respectively), and in those over 50 years old compared to those under 50 years of age (19.3 ng/mL vs. 16.2 ng/mL, p < 0.001, respectively). In this study, significant positive associations were found between the plasma level of FABP4 and obesity markers: BMI (r = 0.496, p < 0.001), hip circumference (r = 0.463, p < 0.001), and waist circumference (WC) (r = 0.436, p < 0.001). Similar observations were also seen with glycemic markers, which included HbA1c (r = 0.126, p < 0.001), fasting blood glucose (FBG) (r = 0.184, p < 0.001), fasting insulin (r = 0.326, p < 0.001), and HOMA-IR (r = 0.333, p < 0.001). Importantly, these associations remained significant even after adjusting for age, gender, and ethnicity. Furthermore, FABP4 levels were negatively associated with male gender (ß: -3.85, 95% CI: -4.92, -2.77, p < 0.001), and positively associated with age (ß: 0.14, 95% CI: 0.096, 0.183, p < 0.001), BMI (ß: 0.74, 95% CI: 0.644, 0.836, p < 0.001), and fasting insulin (ß: 0.115, 95% CI: 0.091, 0.138, p < 0.001). In this study, plasma FABP4 levels were significantly higher in diabetic and obese participants, and they were strongly influenced by age, gender, and ethnicity. These findings suggest that FABP4 may serve as a valuable prognostic and diagnostic marker for obesity and diabetes, particularly among female patients, individuals over 50 years old, and specific ethnic groups.


Asunto(s)
Proteínas de Unión a Ácidos Grasos , Obesidad , Humanos , Proteínas de Unión a Ácidos Grasos/sangre , Proteínas de Unión a Ácidos Grasos/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/metabolismo , Adulto , Estudios de Cohortes , Factores de Edad , Anciano , Etnicidad , Índice de Masa Corporal , Biomarcadores/sangre , Diabetes Mellitus/sangre , Diabetes Mellitus/metabolismo , Glucemia/metabolismo
20.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38731880

RESUMEN

Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future.


Asunto(s)
Tejido Adiposo , Obesidad , Humanos , Animales , Obesidad/metabolismo , Tejido Adiposo/metabolismo , Adipoquinas/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Microbioma Gastrointestinal , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Mediadores de Inflamación/metabolismo , Metabolismo Energético
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