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3.
Expert Opin Drug Metab Toxicol ; 18(5): 323-335, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35815356

RESUMO

INTRODUCTION: Vancomycin dosing decisions are informed by factors such as body weight and renal function. It is important to understand the impact of obesity on vancomycin pharmacokinetics and how this may influence dosing decisions. Vancomycin dosing guidelines use varied descriptors of body weight and renal function. There is uncertainty whether current dosing guidelines result in attainment of therapeutic targets in obese individuals. AREAS COVERED: Literature was explored using PubMed, Embase, and Google Scholar for articles from January 1980 to July 2021 regarding obesity-driven physiological changes, their influence on vancomycin pharmacokinetics and body size descriptors and renal function calculations in vancomycin dosing. Pharmacokinetic simulations reflective of international vancomycin dosing guidelines were conducted to evaluate the ability of using total, ideal, and adjusted body weight, as well as Cockcroft-Gault and CKD-EPI equations to attain an area-under-the-curve to minimum inhibitory concentration ratio (AUC24/MIC) target (400-650) in obese individuals. EXPERT OPINION: Vancomycin pharmacokinetics in obese individuals remains debated. Guidelines that determine loading doses using total body weight, and maintenance doses adjusted based on renal function and adjusted body weight, may be most appropriate for obese individuals. Use of ideal body weight leads to subtherapeutic vancomycin exposure and underestimation of renal function.


Assuntos
Obesidade , Vancomicina , Humanos , Obesidade/tratamento farmacológico , Obesidade/fisiopatologia , Guias de Prática Clínica como Assunto , Vancomicina/administração & dosagem , Vancomicina/farmacocinética
4.
Exp Physiol ; 107(8): 965-977, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35771362

RESUMO

NEW FINDINGS: What is the central question of the study? What are the sex differences in ventilatory responses during exercise in adults with obesity? What is the main finding and its importance? Tidal volume and expiratory flows are lower in females when compared with males at higher levels of ventilation despite small increases in end-expiratory lung volumes. Since dyspnoea on exertion is a frequent complaint, particularly in females with obesity, careful attention should be paid to unpleasant respiratory symptoms and mechanical ventilatory constraints while prescribing exercise. ABSTRACT: Obesity is associated with altered ventilatory responses, which may be exacerbated in females due to the functional consequences of sex-related morphological differences in the respiratory system. This study examined sex differences in ventilatory responses during exercise in adults with obesity. Healthy adults with obesity (n = 73; 48 females) underwent pulmonary function testing, underwater weighing, magnetic resonance imaging (MRI), a graded exercise test to exhaustion, and two constant work rate exercise tests; one at a fixed work rate (60 W for females and 105 W for males) and one at a relative intensity (50% of peak oxygen uptake, V ̇ O 2 peak ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ ). Metabolic, respiratory and perceptual responses were assessed during exercise. Compared with males, females used a smaller proportion of their ventilatory capacity at peak exercise (69.13 ± 14.49 vs. 77.41 ± 17.06% maximum voluntary ventilation, P = 0.0374). Females also utilized a smaller proportion of their forced vital capacity (FVC) at peak exercise (tidal volume: 48.51 ± 9.29 vs. 54.12 ± 10.43%FVC, P = 0.0218). End-expiratory lung volumes were 2-4% higher in females compared with males during exercise (P < 0.05), while end-inspiratory lung volumes were similar. Since the males were initiating inspiration from a lower lung volume, they experienced greater expiratory flow limitation during exercise. Ratings of perceived breathlessness during exercise were similar between females and males at comparable levels of ventilation. In summary, sex differences in the manifestations of obesity-related mechanical ventilatory constraints were observed. Since dyspnoea on exertion is a common complaint in patients with obesity, particularly in females, exercise prescriptions should be tailored with the goal of minimizing unpleasant respiratory sensations.


Assuntos
Exercício Físico/fisiologia , Obesidade/terapia , Caracteres Sexuais , Adulto , Dispneia , Teste de Esforço , Feminino , Humanos , Masculino , Obesidade/fisiopatologia , Ventilação Pulmonar , Respiração Artificial , Volume de Ventilação Pulmonar
5.
Bol. malariol. salud ambient ; 62(1): 32-38, jun, 2022. tab, ilus
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1379293

RESUMO

Hay dos tipos principales de tejido adiposo; el subcutáneo, que es menos activo metabólicamente, y el tejido adiposo visceral, que secreta constantemente citocinas inflamatorias y está relacionado a enfermedades metabólicas y cardiovasculares. Nuestro objetivo fue identificar la asociación entre el exceso de grasa visceral y la severidad de enfermedad en pacientes con COVID-19. Se realizó un estudio observacional analítico que incluyó a pacientes con COVID-19 admitidos al Hospital Carrión de Huancayo, Perú. Se utilizó la balanza de bioimpedancia para cuantificar la composición corporal, la variable dependiente fue la severidad de enfermedad. Se utilizó el análisis de regresión logística para determinar la asociación de la grasa visceral y otros parámetros antropométricos con severidad de enfermedad. Se analizaron a 120 personas con COVID-19, la edad promedio fue 50 años, el sexo masculino fue 60%. De acuerdo a los valores de la composición corporal emitidos por el equipo de bioimpedancia: La grasa visceral > 15Kg (OR 7,31; p = 0,001); la grasa corporal total > 35% (OR 5,58; p = 0,009) y el exceso de peso > 20Kg (OR 6,96; p = 0,011) fueron los parámetros asociados a enfermedad severa por COVID-19. La relación positiva entre el perímetro abdominal y la cantidad de grasa visceral fue significativo (p = 0,01). En la composición corporal, el exceso de grasa visceral es el mayor parámetro asociado a enfermedad severa por COVID-19(AU)


There are two main types of adipose tissue; the subcutaneous, which is less metabolically active, and the visceral adipose tissue, which constantly secretes inflammatory cytokines and is related to metabolic and cardiovascular diseases. Our objetive was to identify the association between the excess of visceral fat and disease severity in COVID-19 patients. An analytical observational study was carried out which included patients with COVID-19 admitted to the Carrión Hospital in Huancayo, Peru. The bioimpedance balance was used to quantify the body composition; the dependent variable was the severity of the disease. A logistic regression analysis was used to determine the association of visceral fat and other anthropometric parameters with the severity of the disease. Out of 120 people with COVID-19 were analyzed, the average age was 50 years, the male sex was 60%. According to the body composition values issued by the bioimpedance team: Visceral fat> 15Kg (OR 7.31; p = 0.001); Total body fat> 35% (OR 5.58; p = 0.009) and excess weight> 20Kg (OR 6.96; p = 0.011) were the parameters associated with severe disease due to COVID-19. The positive relationship between abdominal circumference and the amount of visceral fat was significant (p = 0.01). In body composition, excess visceral fat is the main parameter associated with severe COVID-19 disease(AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Gordura Intra-Abdominal/fisiopatologia , COVID-19/fisiopatologia , COVID-19/epidemiologia , Obesidade/fisiopatologia , Peru/epidemiologia , Índice de Gravidade de Doença , Índice de Massa Corporal , Modelos Logísticos , Análise de Regressão , Hospitais
6.
J. oral res. (Impresa) ; 11(1): 1-11, may. 11, 2022. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1399662

RESUMO

Introduction: Chewing is a learned orofacial function, important in the nutrition process of most mammals. It has been described that it can vary according to the characteristics of the individuals and the characteristics of the food. The aim of this study was to compare the kinematic characteristics of mastication in subjects with different body mass index (BMI), including foods of different hardness in the analysis. Material and Methods: A cross-sectional observational study was conducted. The mastication of 3.7 g of peanut (soft food) and 3.7 g of carrot (hard food) was compared among three study groups formed according to BMI: normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9) and obese (BMI ≥30); each with 7 participants. The kinematics of the masticatory movement were assessed with a 3D Electromagnetic Articulograph, the characteristics analyzed were number of masticatory cycles, masticatory frequency, speed and area of the cycles. Results: No significant differences were noted among the study groups for the number of masticatory cycles, frequency or speed in the two foods studied. It was observed that when chewing carrot, the horizontal area of the masticatory cycles was significantly larger in the obese than in the overweight group. However, when chewing peanuts, this parameter did not present significant differences among the different groups. A comparison of the characteristics of mastication of the two foods revealed that the carrot chewing presented a significantly greater masticatory frequency and speed than the peanut chewing. Conclusion: This study demonstrated that food hardness influences the kinematic characteristics of mastication more than BMI, noting that hard foods are masticated faster and more frequently than soft foods and that masticatory frequency tends to increase with BMI.


Introduction: Chewing is a learned orofacial function, important in the nutrition process of most mammals. It has been described that it can vary according to the characteristics of the individuals and the characteristics of the food. The aim of this study was to compare the kinematic cha-racteristics of mastication in subjects with different body mass index (BMI), including foods of different hardness in the analysis. Material and Methods: A cross-sectional observational study was con- ducted. The mastication of 3.7 g of peanut (soft food) and 3.7 g of carrot (hard food) was compared among three study groups formed according to BMI: normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9) and obese (BMI ?30); each with 7 participants. The kinematics of the masticatory movement were assessed with a 3D Electromagnetic Articulograph, the characteristics analyzed were number of masticatory cycles, masticatory frequency, speed and area of the cycles. Results: No significant differences were noted among the study groups for the number of masticatory cycles, frequency or speed in the two foods studied. It was observed that when chewing carrot, the horizontal area of the masticatory cycles was significantly larger in the obese than in the overweight group. However, when chewing peanuts, this parameter did not present significant differences among the different groups. A comparison of the characteristics of mastication of the two foods revealed that the carrot chewing presented a significantly greater masticatory frequency and speed than the peanut chewing. Conclusion: This study demonstrated that food hardness influences the kinematic characteristics of mastication more than BMI, noting that hard foods are masticated faster and more frequently than soft foods and that masticatory frequency tends to increase with BMI.


Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Peso Corporal/fisiologia , Índice de Massa Corporal , Mastigação/fisiologia , Fenômenos Biomecânicos , Sobrepeso/fisiopatologia , Alimentos , Obesidade/fisiopatologia
7.
Nutr. hosp ; 39(2): 320-328, mar.- abr. 2022. tab, graf
Artigo em Inglês | IBECS | ID: ibc-209700

RESUMO

Introduction: central obesity is associated with an autonomic dysfunction characterized by an increase in sympathetic activity and a reduction in vagal tone, leading to a decrease in heart rate variability. Objective: we aimed to analyze the relationship between the time and frequency domains of heart rate variability with central obesity, and its hemodynamic variables in normal-weight, overweight and obese adults. Methods: a total of 65 adults were evaluated (25.4 ± 3.2 years old) and distributed in 3 groups: normal weight group (NW group), overweight group (OW group) and obese group (OB group). Heart rate variability parameters at rest and both anthropometric and hemodynamic variables were recorded. Results: the results showed a positive correlation between waist circunference and LF/HF ratio in the OW (p = 0.0008; r = 0.6607; r2 = 0.4365) and OB (p = 0.0001; r = 0.8286; r2 = 0.6866) groups. The waist-to-height ratio showed significant differences with HF in the NW, OW, and OB groups. The variables related to the parasympathetic system (SDNN, RMSSD, pNN50, HF) in the OB and OW groups showed a decrease in values when compared to the NW group. Likewise, the variable related to the sympathetic system (LF) in the OB and OW groups increased its values when compared with the NW group. The LF/HF ratio increased from the NW group to the OW and OB groups (1.6 ± 0.7; 2.5 ± 1.8 and 3.3 ± 0.7). Conclusion: overweight and obese adults present a modulation of sympathetic activity predominance at rest. This increased activity is represented by the time and frequency domains of heart rate variability, having an important correlation with waist circumference and waist-to-height ratio (AU)


Introducción: la obesidad central se asocia con una disfunción autonómica caracterizada por una mayor actividad simpática y reducción del tono vagal, conduciendo a una disminución de la variabilidad de la frecuencia cardíaca (VFC). Objetivo: analizar la relación entre los dominios de tiempo y frecuencia de la VFC con la obesidad central y sus variables hemodinámicas en adultos con peso normal, sobrepeso y obesidad. Metodología: participaron 65 adultos (25,4 ± 3,2 años) distribuidos en 3 grupos: peso normal (grupo NW), sobrepeso (grupo OW) y obesidad (grupo OB). Se registraron los parámetros de la VFC y las variables antropométricas y hemodinámicas. Resultados: se observó una correlación positiva entre la circunferencia de la cintura y la relación LF/HF en el grupo OW (p = 0,0008; r = 0,6607; r2 = 0,4365) y OB (p = 0,0001; r = 0,8286; r2 = 0,6866). La relacion cintura/altura mostró una diferencia significativa con la HF en los grupos NW, OW y OB. La actividad parasimpática (SDNN, RMSSD, pNN50, HF) de los grupos OB y OW evidenció una disminución de los valores en comparación con el grupo NW. La actividad simpática (LF) en el grupo OB y OW presentó mayores valores que en el grupo NW. La relación LF/HF aumentó del grupo NW hacia el OW y el OB (1,6 ± 0,7; 2,5 ± 1,8 y 3,3 ± 0,7). Conclusiones: el sobrepeso y la obesidad presentan una predominancia de la actividad simpática en reposo. Este aumento de la actividad está representado en el dominio de tiempo y frecuencia de la VFC y, además, presenta una correlación importante con la circunferencia de la cintura y la relación cintura/altura (AU)


Assuntos
Humanos , Masculino , Adulto Jovem , Adulto , Sistema Nervoso Autônomo/fisiologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Índice de Massa Corporal , Frequência Cardíaca , Estudos Prospectivos
8.
J Diabetes Res ; 2022: 9321445, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242881

RESUMO

Obesity and dyslipidemias are both signs of metabolic syndrome, usually associated with ventricular arrhythmias. Here, we tried to identify cardiac electrical alteration and biomarkers in nonobese rats with metabolic syndrome (MetS), and these findings might lead to more lethal arrhythmias than obese animals. The MetS model was developed in Wistar rats with high-sucrose diet (20%), and after twenty-eight weeks were obtained two subgroups: obese (OMetS) and nonobese (NOMetS). The electrocardiogram was used to measure the ventricular arrhythmias and changes in the heart rate variability. Also, we measured ventricular hypertrophy and its relationship with electrical activity alterations of both ventricles, using micro-electrode and voltage clamp techniques. Also, we observed alterations in the contraction force of ventricles where a transducer was used to record mechanical and electrical papillary muscle, simultaneously. Despite both subgroups presenting long QT syndrome (0.66 ± 0.05 and 0.66 ± 0.07 ms with respect to the control 0.55 ± 0.1 ms), the changes in the heart rate variability were present only in OMetS, while the NOMetS subgroup presented changes in QT interval variability (NOMetS SD = 1.8, SD2 = 2.8; SD1/SD2 = 0.75). Also, the NOMetS revealed tachycardia (10%; p < 0.05) with changes in action potential duration (63% in the right papillary and 50% in the left papillary) in the ventricular papillary which are correlated with certain alterations in the potassium currents and the force of contraction. The OMetS showed an increase in action potential duration and the force of contraction in both ventricles, which are explained as bradycardia. Our results revealed lethal arrhythmias in both MetS subgroups, irrespectively of the presence of obesity. Consequently, the NOMetS showed mechanical-electrical alterations regarding ventricle hypertrophy that should be at the NOMetS, leading to an increase of CV mortality.


Assuntos
Síndrome Metabólica/complicações , Obesidade/complicações , Disfunção Ventricular/fisiopatologia , Animais , Modelos Animais de Doenças , Síndrome Metabólica/fisiopatologia , Obesidade/fisiopatologia , Ratos , Ratos Wistar/metabolismo , Disfunção Ventricular/etiologia
9.
Endocrine ; 76(3): 558-569, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35229234

RESUMO

PURPOSE: Approximately 650 million of world adult population is affected by obesity, which is characterized by adipose and hepatic metabolic dysfunction. Short chain fatty acids (SCFAs) have been linked to improved metabolic profile. However, the effect of SCFAs, particularly acetate on adipose-hepatic dysfunction is unclear. Therefore, the present study investigated the role of acetate on adipose-hepatic metabolic dysfunction and the possible involvement of obestatin in high fat diet-induced obese Wistar rats. METHODS: Adult male Wistar rats (160-190 g) were allotted into groups (n = 6/group): Control, acetate-treated, obese and obese + acetate-treated groups received vehicle (distilled water), sodium acetate (200 mg/kg), 40% HFD and 40% HFD plus sodium acetate respectively. The administration lasted for 12 weeks. RESULTS: HFD caused increased body weight gain and visceral adiposity, insulin resistance, hyperinsulinemia and increased pancreatic-ß cell function and plasma/hepatic triglyceride and total cholesterol as well as decreased adipose triglyceride and total cholesterol, increased plasma, adipose, and hepatic malondialdehyde, TNF-α, uric acid, lactate production and plasma/adipose but not gamma-glutamyl transferase and decreased plasma, adipose, and hepatic nitric oxide, glucose-6-phosphate dehydrogenase (G6PD), glutathione (GSH) and obestatin concentration compared to the control group. Notwithstanding, treatment with acetate attenuated the alterations. CONCLUSIONS: The results demonstrate that high fat diet-induced obesity is characterized with adipose and hepatic lipid dysmetabolism, which is associated with obestatin suppression. Findings also suggest that acetate provide protection against adipose and hepatic metabolic perturbations by restoring obestatin as well as G6PD/GSH-dependent antioxidant system.


Assuntos
Dieta Hiperlipídica , Grelina , Resistência à Insulina , Obesidade , Acetato de Sódio , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Grelina/metabolismo , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Ratos , Ratos Wistar , Acetato de Sódio/farmacologia , Triglicerídeos/metabolismo
10.
BMC Cancer ; 22(1): 232, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35255844

RESUMO

BACKGROUND: Greater early life adiposity has been reported to reduce postmenopausal breast cancer risk but it is unclear whether this association varies by tumour characteristics. We aimed to assess associations of early life body size with postmenopausal breast cancer and its subtypes, allowing for body size at other ages. METHODS: A total of 342,079 postmenopausal UK women who reported their body size at age 10, clothes size at age 20, and body mass index (BMI) at baseline (around age 60) were followed by record linkage to national databases for cancers and deaths. Cox regression yielded adjusted relative risks (RRs) of breast cancer, overall and by tumour subtype, in relation to body size at different ages. RESULTS: During an average follow-up of 14 years, 15,506 breast cancers were diagnosed. After adjustment for 15 potential confounders, greater BMI at age 60 was associated with an increased risk of postmenopausal breast cancer (RR per 5 kg/m2=1.20, 95%CI 1.18-1.22) whereas greater adiposity in childhood and, to a lesser extent, early adulthood, was associated with a reduced risk (0.70, 0.66-0.74, and 0.92, 0.89-0.96, respectively). Additional adjustment for midlife BMI strengthened associations with BMI at both age 10 (0.63, 0.60-0.68) and at age 20 (0.78, 0.75-0.81). The association with midlife adiposity was confined to hormone sensitive subtypes but early life adiposity had a similar impact on the risk of all subtypes. CONCLUSION: Early life and midlife adiposity have opposite effects on postmenopausal breast cancer risk and the biological mechanisms underlying these associations are likely to differ.


Assuntos
Adiposidade , Tamanho Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Obesidade/complicações , Índice de Massa Corporal , Criança , Feminino , Seguimentos , Humanos , Registro Médico Coordenado , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Pós-Menopausa , Modelos de Riscos Proporcionais , Fatores de Risco , Reino Unido/epidemiologia , Adulto Jovem
11.
Int J Mol Sci ; 23(5)2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35269594

RESUMO

The abnormal accumulation of methylglyoxal (MG) leading to increased glycation of protein and DNA has emerged as an important metabolic stress, dicarbonyl stress, linked to aging, and disease. Increased MG glycation produces inactivation and misfolding of proteins, cell dysfunction, activation of the unfolded protein response, and related low-grade inflammation. Glycation of DNA and the spliceosome contribute to an antiproliferative and apoptotic response of high, cytotoxic levels of MG. Glyoxalase 1 (Glo1) of the glyoxalase system has a major role in the metabolism of MG. Small molecule inducers of Glo1, Glo1 inducers, have been developed to alleviate dicarbonyl stress as a prospective treatment for the prevention and early-stage reversal of type 2 diabetes and prevention of vascular complications of diabetes. The first clinical trial with the Glo1 inducer, trans-resveratrol and hesperetin combination (tRES-HESP)-a randomized, double-blind, placebo-controlled crossover phase 2A study for correction of insulin resistance in overweight and obese subjects, was completed successfully. tRES-HESP corrected insulin resistance, improved dysglycemia, and low-grade inflammation. Cell permeable Glo1 inhibitor prodrugs have been developed to induce severe dicarbonyl stress as a prospective treatment for cancer-particularly for high Glo1 expressing-related multidrug-resistant tumors. The prototype Glo1 inhibitor is prodrug S-p-bromobenzylglutathione cyclopentyl diester (BBGD). It has antitumor activity in vitro and in tumor-bearing mice in vivo. In the National Cancer Institute human tumor cell line screen, BBGD was most active against the glioblastoma SNB-19 cell line. Recently, potent antitumor activity was found in glioblastoma multiforme tumor-bearing mice. High Glo1 expression is a negative survival factor in chemotherapy of breast cancer where adjunct therapy with a Glo1 inhibitor may improve treatment outcomes. BBGD has not yet been evaluated clinically. Glycation by MG now appears to be a pathogenic process that may be pharmacologically manipulated for therapeutic outcomes of potentially important clinical impact.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glutationa/análogos & derivados , Hesperidina/uso terapêutico , Lactoilglutationa Liase/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Quimioterapia Combinada , Indução Enzimática/efeitos dos fármacos , Glutationa/química , Glutationa/uso terapêutico , Glicosilação/efeitos dos fármacos , Hesperidina/química , Humanos , Resistência à Insulina/fisiologia , Lactoilglutationa Liase/antagonistas & inibidores , Camundongos , Estrutura Molecular , Neoplasias Experimentais/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/fisiopatologia , Aldeído Pirúvico/química , Aldeído Pirúvico/metabolismo , Resveratrol/química
12.
Reprod Biol Endocrinol ; 20(1): 33, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35183196

RESUMO

BACKGROUND: Growing evidence suggests that adherence to certain dietary patterns is associated with improved fecundity and reproductive outcomes in the general population and infertile couples assisted reproductive treatments. The objective of this study was to assess if dietary patterns are associated with ovarian reserve in reproductive age women without a history of infertility. METHODS: This was a cross-sectional study of 185 women in the Lifestyle and Ovarian Reserve (LORe) cohort. Women aged 18-44 without a history of infertility were recruited from the local community at an academic medical center. Subjects completed validated food frequency and physical activity questionnaires to assess patterns over the year prior to presentation. Dietary patterns including a Western (including meat, refined carbohydrates, high-calorie drinks), prudent (including fruits, vegetables, olive oil and nuts), fertility (lower intake of trans fat with higher intake of monounsaturated fatty acids, increased intake of plant based protein, high-fat dairy, lower glycemic load carbohydrates and supplemental iron) and profertility diet (PFD) (characterize by whole grains, soy and seafood, low pesticide residue produce, supplemental folic acid, B12 and vitamin D) were identified through principal component analysis. Main outcome measures were serum antimullerian hormone concentration (AMH) (ng/mL) and antral follicle count (AFC) obtained by transvaginal ultrasound. RESULTS: After stratifying by BMI, adjusting for age, smoking and physical activity, dietary patterns were not associated with ovarian reserve in normal weight women. Increased adherence to a profertility diet in overweight and obese women (BMI ≥ 25 kg/m2) was associated with a significantly higher AMH. Women in the third and fourth quartiles of PFD adherence had a mean AMH concentration of 1.45 ng/mL (95%CI 0.33-2.56, p = 0.01) and 1.67 ng/mL (95%CI 0.60-2.74, p = 0.003) higher than women in the lowest quartile respectively. The highest adherence to PFD was also associated with a higher AFC in women with a BMI ≥ 25 kg/m2 (ß = 7.8, 95%CI 0.003-15.34, p < 0.05). Other common dietary patterns were not significantly associated with ovarian reserve. CONCLUSIONS: Increased adherence to a profertility diet is associated with improved markers of ovarian reserve in overweight and obese women. These findings provide novel insight on potential modifiable lifestyle factors associated with ovarian reserve.


Assuntos
Comportamento Alimentar/fisiologia , Obesidade/epidemiologia , Reserva Ovariana/fisiologia , Sobrepeso/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Estudos Transversais , Dieta/estatística & dados numéricos , Feminino , Humanos , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/etiologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
13.
Int J Mol Sci ; 23(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35216332

RESUMO

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Neoplasias da Próstata/microbiologia , Neoplasias da Próstata/fisiopatologia , Animais , Clostridiales/fisiologia , Gorduras Insaturadas na Dieta/metabolismo , Ácidos Graxos/metabolismo , Fezes/microbiologia , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/fisiopatologia , Neoplasias da Próstata/metabolismo , Aumento de Peso/fisiologia
15.
Cells ; 11(3)2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-35159367

RESUMO

Obesity-associated metabolic disorders are rising to pandemic proportions; hence, there is an urgent need to identify underlying molecular mechanisms. Glycogen synthase kinase-3 (GSK-3) signaling is highly implicated in metabolic diseases. Furthermore, GSK-3 expression and activity are increased in Type 2 diabetes patients. However, the isoform-specific role of GSK-3 in obesity and glucose intolerance is unclear. Pharmacological GSK-3 inhibitors are not isoform-specific, and tissue-specific genetic models are of limited value to predict the clinical outcome of systemic inhibiion. To overcome these limitations, we created novel mouse models of ROSA26CreERT2-driven, tamoxifen-inducible conditional deletion of GSK-3 that allowed us to delete the gene globally in an isoform-specific and temporal manner. Isoform-specific GSK-3 KOs and littermate controls were subjected to a 16-week high-fat diet (HFD) protocol. On an HFD, GSK-3α KO mice had a significantly lower body weight and modest improvement in glucose tolerance compared to their littermate controls. In contrast, GSK-3ß-deletion-mediated improved glucose tolerance was evident much earlier in the timeline and extended up to 12 weeks post-HFD. However, this protective effect weakened after chronic HFD (16 weeks) when GSK-3ß KO mice had a significantly higher body weight compared to controls. Importantly, GSK-3ß KO mice on a control diet maintained significant improvement in glucose tolerance even after 16 weeks. In summary, our novel mouse models allowed us to delineate the isoform-specific role of GSK-3 in obesity and glucose tolerance. From a translational perspective, our findings underscore the importance of maintaining a healthy weight in patients receiving lithium therapy, which is thought to work by GSK-3 inhibition mechanisms.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/etiologia , Quinase 3 da Glicogênio Sintase/efeitos adversos , Obesidade/etiologia , Isoformas de Proteínas/metabolismo , Animais , Feminino , Intolerância à Glucose/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Obesidade/fisiopatologia
16.
Cell Mol Life Sci ; 79(3): 139, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-35184223

RESUMO

The adipose organ comprises two main fat depots termed white and brown adipose tissues. Adipogenesis is a process leading to newly differentiated adipocytes starting from precursor cells, which requires the contribution of many cellular activities at the genome, transcriptome, proteome, and metabolome levels. The adipogenic program is accomplished through two sequential phases; the first includes events favoring the commitment of adipose tissue stem cells/precursors to preadipocytes, while the second involves mechanisms that allow the achievement of full adipocyte differentiation. While there is a very large literature about the mechanisms involved in terminal adipogenesis, little is known about the first stage of this process. Growing interest in this field is due to the recent identification of adipose tissue precursors, which include a heterogenous cell population within different types of adipose tissue as well as within the same fat depot. In addition, the alteration of the heterogeneity of adipose tissue stem cells and of the mechanisms involved in their commitment have been linked to adipose tissue development defects and hence to the onset/progression of metabolic diseases, such as obesity. For this reason, the characterization of early adipogenic events is crucial to understand the etiology and the evolution of adipogenesis-related pathologies, and to explore the adipose tissue precursors' potential as future tools for precision medicine.


Assuntos
Adipócitos Brancos/citologia , Adipogenia , Diferenciação Celular , Obesidade/fisiopatologia , Termogênese , Animais , Humanos
17.
Life Sci ; 296: 120425, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35202642

RESUMO

AIMS: The association between asthma and obesity has been shown but its accurate mechanism is unknown. In the current study, we sought to investigate the gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine level (IL-6, IL-1ß, and TNF-α) in obese Ovalbumin (OVA)-sensitized female and male Wistar rats lung tissue. MAIN METHODS: Animals in both males and females were divided into eight groups (four groups in each sex) based on diet and OVA-sensitization: normal diet, a normal diet with OVA-sensitization, high-fat diet (HFD), and OVA-sensitization with an HFD. KEY FINDINGS: In both sexes, obese OVA-sensitized rats, the methacholine concentration-response curve shifted to the left and EC50 methacholine decreased. Increased pro-inflammatory cytokines as well as elevated IL-17/TRAF6/MAPK axis genes and decreased USP25 gene expression were identified in obese OVA-sensitized groups. SIGNIFICANCE: The results indicate that in obese OVA-sensitized rats, the IL-17 axis were involved in the pathogenesis of the disease and can be considered as a therapeutic target in subjects with obesity-related asthma.


Assuntos
Interleucina-17/genética , Pulmão/fisiologia , Obesidade/genética , Fator 6 Associado a Receptor de TNF/genética , Ubiquitina Tiolesterase/genética , Animais , Peso Corporal/genética , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica , Pulmão/fisiopatologia , Masculino , Cloreto de Metacolina/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Obesidade/fisiopatologia , Ovalbumina/toxicidade , Ratos Wistar , Traqueia/efeitos dos fármacos
18.
Int J Mol Sci ; 23(4)2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35216423

RESUMO

The prevalence of obesity has reached pandemic levels and is becoming a serious health problem in developed and developing countries. Obesity is associated with an increased prevalence of comorbidities that include type II diabetes, cardiovascular diseases and some cancers. The recognition of adipose tissue as an endocrine organ capable of secreting adipokines that influence whole-body energy homeostasis was a breakthrough leading to a better molecular understanding of obesity. Of the adipokines known to be involved in the regulation of energy metabolism, very few are considered central regulators of insulin sensitivity, metabolism and energy homeostasis, and the discovery and characterization of new adipocyte-derived factors are still ongoing. Proteomics techniques, such as liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry, have proven to be useful tools for analyzing the secretory function of adipose tissue (the secretome), providing insights into molecular events that influence body weight. Apart from the identification of novel proteins, the considerable advantage of this approach is the ability to detect post-translational modifications that cannot be predicted in genomic studies. In this review, we summarize recent efforts to identify novel bioactive secretory factors through proteomics.


Assuntos
Tecido Adiposo/fisiologia , Células Endócrinas/fisiologia , /fisiologia , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Metabolismo Energético/fisiologia , Humanos , Obesidade/fisiopatologia
19.
Sci Rep ; 12(1): 2410, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165286

RESUMO

The present study aimed to distinguish different hypertriglyceridemic waist phenotypes and relevant risks of developing fatty liver and abnormal glycometabolic profiles in overweight/obese adults. A total of 1221 Chinese adults with mean (standard deviation [SD]) age of 37 (9) years, 37.3% males and 62.7% females, body mass index (BMI) of 29.0 (4.0) kg/m2, triglyceride (TG) 2.04 (1.45) mmol/L, and waist circumference (WC) 95.8 (10.7) cm were included and classified into four phenotypes: normal TG & normal WC (N-N); normal TG & high WC (N-WC); high TG & normal WC (TG-N); high TG & high WC (TG-WC). Participants in TG-WC group had the highest BMI, WC, blood pressure (BP), insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL), and fatty liver. Participants within N-WC group had a significantly higher risk of fatty liver (adjusted OR 3.50 [95% CI 2.05-5.97]), as well as TG-N (adjusted OR 2.59 [95% CI 1.61-4.16]) and TG-WC (adjusted OR 4.12 [95% CI 2.28-7.46]). The risk of elevated HOMA-IR was significantly higher in TG-N (adjusted OR 2.16 [95% CI 1.33-3.50]) and TG-WC (adjusted OR 2.04 [95% CI 1.22-3.40]). The risk of elevated HbA1c was significantly higher in the TG-WC (adjusted OR 2.79 [95% CI 1.47-5.31]). Hypertriglyceridemic waist phenotype can be a potential and cost-effective method to identify individuals with a high risk of fatty liver and glycometabolic disorders.


Assuntos
Fígado Gorduroso/etiologia , Obesidade/complicações , Sobrepeso/complicações , Triglicerídeos/sangue , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , China , HDL-Colesterol/sangue , Estudos Transversais , Fígado Gorduroso/metabolismo , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Cintura Hipertrigliceridêmica , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Fenótipo , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
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