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1.
Nat Commun ; 11(1): 4718, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948777

RESUMO

Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-κB pathways, and thus stimulates naïve and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Linfócitos/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Adipócitos/metabolismo , Adolescente , Adulto , Idoso , Animais , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Feminino , Glucose/metabolismo , Homeostase , Humanos , Imunidade Inata , Resistência à Insulina , Interleucina-33/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/complicações , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Membro 25 de Receptores de Fatores de Necrose Tumoral/uso terapêutico , Adulto Jovem
2.
Am J Clin Nutr ; 112(4): 979-990, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32766878

RESUMO

BACKGROUND: Adipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue-specific roles in systemic metabolic perturbations. OBJECTIVE: We sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications. METHODS: Paired visceral and subcutaneous adipose tissue samples were obtained from 17 overweight patients undergoing elective abdominal surgery. Ultra-performance LC-MS was used to measure 18,640 adipose-derived features; 520 were putatively identified. A stem cell model for adipogenesis was used to study the functional implications of the differences found. RESULTS: Our analyses resulted in detailed lipid metabolic maps of the 2 major adipose tissues. They point to a higher accumulation of phosphatidylcholines, triacylglycerols, and diacylglycerols, although lower ceramide concentrations, in subcutaneous tissue. The degree of unsaturation was lower in visceral adipose tissue (VAT) phospholipids, indicating lower unsaturated fatty acid incorporation into adipose tissue. The differential abundance of phosphatidylcholines we found can be attributed at least partially to higher expression of phosphatidylethanolamine methyl transferase (PEMT). PEMT-deficient embryonic stem cells showed a dramatic decrease in adipogenesis, and the resulting adipocytes exhibited lower accumulation of lipid droplets, in line with the lower concentrations of glycerolipids in VAT. Ceramides may inhibit the expression of PEMT by increased insulin resistance, thus potentially suggesting a functional pathway that integrates ceramide, PEMT, and glycerolipid biosynthetic pathways. CONCLUSIONS: Our work unveils differential infrastructure of the lipid networks in visceral and subcutaneous adipose tissues and suggests an integrative pathway, with a discriminative flux between adipose tissues.


Assuntos
Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos , Sobrepeso/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Animais , Feminino , Glicerofosfolipídeos/metabolismo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Triglicerídeos/metabolismo
3.
Nutr Metab Cardiovasc Dis ; 30(10): 1751-1757, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32811739

RESUMO

BACKGROUND AND AIMS: The assessment of visceral adiposity is of great significance for the prevention of hyperuricemia (HUA), especially in non-obese individuals. The metabolic score for visceral fat (METS-VF) is a newly proposed surrogate of visceral obesity. We aimed to evaluate the longitudinal associations of METS-VF with the risk of HUA in non-obese adults. METHODS AND RESULTS: A total of 16,058 non-obese adults without HUA were included for this retrospective cohort analyses. The crude incidence rate of HUA in non-obese women and men were 20.9 and 69.6 per 1000 person-years, respectively. The Cox proportional hazards model indicated that METS-VF was significantly associated with the risk of HUA in both genders. Whereas, METS-VF only had the highest HR in women, but not in men. CONCLUSIONS: METS-VF, a novel surrogate of visceral adiposity combined biochemical and anthropometric parameters, age, and gender, could be a useful tool for the hierarchical prevention and management of HUA among non-obese women.


Assuntos
Adiposidade , Metabolismo Energético , Hiperuricemia/sangue , Gordura Intra-Abdominal/metabolismo , Obesidade Abdominal/diagnóstico , Ácido Úrico/sangue , Adulto , Biomarcadores/sangue , China/epidemiologia , Feminino , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Incidência , Gordura Intra-Abdominal/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/metabolismo , Obesidade Abdominal/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
4.
Anim Sci J ; 91(1): e13449, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32815204

RESUMO

Ectopic fats have been recognized as a new risk factor for metabolic syndrome. In obese humans, ectopic fat accumulations are affected by body fat distribution. Intramuscular adipose tissue is categorized as one of the ectopic fats. Japanese black cattle (Wagyu) are characterized by the ability to accumulate high amounts of intramuscular adipose tissue. In Japan, the marbling level is indicated by the beef marbling standard number (BMS No.), which reflects the intramuscular fat content of longissimus muscle. We hypothesized that the intramuscular fat accumulation is affected by the body fat distribution in Wagyu cattle. In this study, we showed that the BMS No. was not correlated with the subcutaneous and visceral adipocyte diameter. In contrast, the BMS No. was positively correlated with intramuscular adipocyte diameter. These results indicate that the intramuscular adipocyte diameter of Wagyu is hypertrophied with an increase in the intramuscular fat accumulation. In addition, we showed that the BMS No. was positively correlated with the subcutaneous fat percentage. In contrast, the BMS No. was negatively correlated with the visceral fat percentage. These results indicate that highly marbled Wagyu cattle have a higher percentage of subcutaneous fat and a lower percentage of visceral fat.


Assuntos
Adipócitos/patologia , Adipogenia , Distribuição da Gordura Corporal , Bovinos/metabolismo , Qualidade dos Alimentos , Gordura Intra-Abdominal/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Carne Vermelha/normas , Gordura Subcutânea/metabolismo , Animais , Masculino
5.
Am J Physiol Endocrinol Metab ; 319(2): E427-E437, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32663100

RESUMO

Menopause is often accompanied by visceral obesity. With the aim of exploring the consequences of ovarian failure on visceral fat, we evaluated the effects of ovariectomy and estrogen replacement on the proteome/phosphoproteome and on the fatty acid profile of the retroperitoneal adipose depot (RAT) of rats. Eighteen 3-mo-old female Wistar rats were either ovariectomized or sham operated and fed with standard chow for 3 mo. A subgroup of ovariectomized rats received estradiol replacement. RAT samples were analyzed with data-independent acquisitions LC-MS/MS, and pathway analysis was performed with the differentially expressed/phosphorylated proteins. RAT lipid profile was analyzed by gas chromatography. Ovariectomy induced high adiposity and insulin resistance and promoted alterations in protein expression and phosphorylation. Pathway analysis showed that five pathways were significantly affected by ovariectomy, namely, metabolism of lipids (including fatty acid metabolism and mitochondrial fatty acid ß-oxidation), fatty acyl-CoA biosynthesis, innate immune system (including neutrophil degranulation), metabolism of vitamins and cofactors, and integration of energy metabolism (including ChREBP activates metabolic gene expression). Lipid profile analysis showed increased palmitic and palmitoleic acid content. The analysis of the data indicated that ovariectomy favored lipogenesis whereas it impaired fatty acid oxidation and induced a proinflammatory state in the visceral adipose tissue. These effects are consistent with the findings of high adiposity, hyperleptinemia, and impaired insulin sensitivity. The observed alterations were partially attenuated by estradiol replacement. The data point to a role of disrupted lipid metabolism in adipose tissue in the genesis of obesity after menopause.


Assuntos
Tecido Adiposo Branco/metabolismo , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/fisiologia , Ovariectomia , Proteômica , Adiposidade/fisiologia , Animais , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Ácidos Graxos/análise , Feminino , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/química , Obesidade , Pós-Menopausa , Ratos , Ratos Wistar
6.
Obesity (Silver Spring) ; 28(7): 1245-1253, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32475048

RESUMO

OBJECTIVE: This study aimed to investigate the effect of exercise intensity on visceral adipose tissue (VAT) and liver fat reduction in patients with coronary artery disease (CAD) over 3 months and the maintenance of improvements over 12 months. METHODS: Forty-two participants with CAD were randomized to three sessions/week of either 4 × 4-minute high-intensity interval training (HIIT) or 40 minutes of usual care moderate-intensity continuous training (MICT) for a 4-week supervised cardiac rehabilitation program, followed by three home-based sessions/week for 11 months. Liver fat (as intrahepatic lipid) and VAT were measured via magnetic resonance techniques. Data are mean change (95% CI). RESULTS: HIIT and MICT significantly reduced VAT over 3 months (-350 [-548 to -153] cm3 vs. -456 [-634 to -278] cm3 ; time × group effect: P = 0.421), with further improvement over 12 months (-545 [-818 to -271] cm3 vs. -521 [-784 to -258] cm3 ; time × group effect: P = 0.577) and no differences between groups. Both groups improved liver fat over 3 months, with HIIT tending to show greater reduction than MICT (-2.8% [-4.0% to -1.6%] vs. -1.4% [-2.4% to -0.4%]; time × group effect: P = 0.077). After 12 months, improvements were maintained to a similar degree. Higher exercise intensity predicted liver fat reduction (ß = -0.3 [-0.7 to 0.0]; P = 0.042). CONCLUSIONS: HIIT and MICT reduced VAT over 3 and 12 months. For liver fat, HIIT tended to provide a slightly greater reduction compared with MICT. These findings support HIIT as a beneficial adjunct or alternative to MICT for reducing visceral and liver fat in patients with CAD.


Assuntos
Tecido Adiposo/metabolismo , Reabilitação Cardíaca/métodos , Doença da Artéria Coronariana/terapia , Treinamento Intervalado de Alta Intensidade/métodos , Gordura Intra-Abdominal/patologia , Fígado/metabolismo , Adiposidade/fisiologia , Idoso , Composição Corporal/fisiologia , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Resultado do Tratamento
7.
PLoS One ; 15(6): e0235174, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574226

RESUMO

AIM: To investigate markers of systemic inflammation in pre- and postmenopausal women and identify possible predictors of systemic inflammation with menopause. METHODS: Cross-sectional study of 69 healthy women between 45- and 60 years. Blood samples were collected to assess leukocyte subsets and plasma cytokines. MRI and DXA scans were performed to assess body composition. Through uni- and multivariate analyses, follicle-stimulating hormone (FSH), visceral fat mass and age were evaluated as predictors of systemic inflammation in relation to menopause. RESULTS: Postmenopausal women tended to have higher leukocyte counts (5.4 x109 vs. 4.9 x109 cells/l, p = 0.05) reflected in increased total lymphocytes (1.8 x109 vs. 1.6 x109 cells/l, p = 0.01) and monocytes (0.5 x109 vs. 0.4 x109 cells/l, p = 0.02), compared to premenopausal women. Increased visceral fat mass was a strong predictor of high leukocyte subsets. Postmenopausal women had higher plasma TNF-α (2.24 vs. 1.91 pg/ml, p = 0.01) and IL-6 (0.45 vs. 0.33 pg/ml, p = 0.004) compared to premenopausal women and high FSH was a significant predictor of increased plasma TNF-α, IL-1ß and IL-6. Menopause was further associated with increased T-cells (1,336 vs. 1,128 cells/µl, p = 0.04) reflected in significantly higher counts of exhausted-, senescent-, and memory CD4+ T-cell subsets. CONCLUSIONS: Menopause is associated with increased systemic inflammation as well as exhausted- and senescent T-cells. We suggest, that both increased visceral fat mass and declining sex hormone levels might contribute to postmenopausal systemic inflammation and calls for further large-scale studies to confirm these findings.


Assuntos
Citocinas/imunologia , Inflamação/imunologia , Pós-Menopausa/imunologia , Subpopulações de Linfócitos T/imunologia , Absorciometria de Fóton/métodos , Composição Corporal , Citocinas/sangue , Citocinas/metabolismo , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/imunologia , Hormônios Esteroides Gonadais/sangue , Hormônios Esteroides Gonadais/imunologia , Humanos , Inflamação/sangue , Inflamação/metabolismo , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/metabolismo , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia , Monócitos/metabolismo , Análise Multivariada , Pós-Menopausa/sangue , Pós-Menopausa/metabolismo , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/metabolismo
8.
Nutr Metab Cardiovasc Dis ; 30(8): 1306-1314, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32507340

RESUMO

BACKGROUND AND AIMS: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance. METHODS AND RESULTS: In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm2 and aSAT of 300 (111) cm2. Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59-70), 33% (95%CI: 28-42) and 20% (95%CI: 14-26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women. CONCLUSION: Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women.


Assuntos
Adiponectina/sangue , Proteína C-Reativa/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Leptina/sangue , Obesidade Abdominal/sangue , Gordura Subcutânea/metabolismo , Adiposidade , Fatores Etários , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/fisiopatologia
9.
Metabolism ; 108: 154261, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32407726

RESUMO

BACKGROUND: Fibronectin type IIIdomain-containing protein 4 (FNDC4) constitutes a secreted factor showing a high homology in the fibronectin type III and transmembrane domains with the exercise-associated myokine irisin (FNDC5). We sought to evaluate whether FNDC4 mimics the anti-obesity effects of FNDC5/irisin in human adipose tissue. METHODS: Plasma and adipose tissue samples of 78 patients with morbid obesity undergoing bariatric surgery and 26 normal-weight individuals were used in the present study. RESULTS: Plasma FNDC4 was decreased in patients with morbid obesity, related to obesity-associated systemic inflammation and remained unchanged six months after bariatric surgery. Visceral adipose tissue from patients with morbid obesity showed higher expression of FNDC4 and its putative receptor GPR116 regardless of the degree of insulin resistance. FNDC4 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human visceral adipocytes. FNDC4 reduced intracytosolic lipid accumulation and stimulated a brown-like pattern in human adipocytes, as evidenced by an upregulated expression of UCP-1 and the brown/beige adipocyte markers PRDM16, TMEM26 and CD137. Moreover, FNDC4 treatment upregulated mitochondrial DNA content and factors involved in mitochondrial biogenesis (TFAM, NRF1 and NRF2). Human FNDC4-knockdown adipocytes exhibited an increase in lipogenesis and a reduction of brown/beige-specific fat markers as well as factors involved in mitochondrial biogenesis. CONCLUSIONS: Taken together, the novel adipokine FNDC4 reduces lipogenesis and increases fat browning in human visceral adipocytes. The upregulation of FNDC4 in human visceral fat might constitute an attempt to attenuate the adipocyte hypertrophy, inflammation and impaired beige adipogenesis in the obese state.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Tecido Adiposo Marrom/metabolismo , Lipogênese/fisiologia , Proteínas/metabolismo , Adipócitos Bege/metabolismo , Células Cultivadas , Estudos Transversais , Feminino , Humanos , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Obesidade/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Proteína Desacopladora 1/metabolismo , Regulação para Cima/fisiologia
10.
Cancer Causes Control ; 31(8): 723-735, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32430684

RESUMO

PURPOSE: Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancer patients. METHODS: Pre-surgery plasma samples from 212 patients (stage I-IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival. RESULTS: In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA: pFDR range 0.017-0.049; TFA: pFDR range 0.029-0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (phet range: 0.00044-0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio [HR], 9.05; 95% confidence interval [CI] 2.17-37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04-0.87; phet = 0.00044). CONCLUSION: These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.


Assuntos
Neoplasias Colorretais/metabolismo , Gordura Intra-Abdominal/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adiposidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Metabolômica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Gordura Subcutânea Abdominal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Chemosphere ; 255: 127000, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417515

RESUMO

BACKGROUND: Bisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood. OBJECTIVE: To determine the impact of prenatal BPA exposure on genome-wide gene expression of VAT and SAT depots. METHODS: RNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Gene expression and pathway differences between SAT and VAT depots with or without prenatal BPA-treatment and the effect of prenatal BPA treatment on each depot were tested. RESULTS: There were 179 differentially expressed genes (padjusted < 0.05, log2-fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. These adipose depot-specific genes and pathways were consistent with prenatal BPA-treatment. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways. CONCLUSION: Prenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin pathways, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.


Assuntos
Adiposidade/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Gordura Subcutânea/efeitos dos fármacos , Adiposidade/genética , Animais , Compostos Benzidrílicos/sangue , Regulação para Baixo , Disruptores Endócrinos/sangue , Feminino , Perfilação da Expressão Gênica , Inflamação , Gordura Intra-Abdominal/crescimento & desenvolvimento , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Fenóis/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , RNA/genética , RNA/metabolismo , Ovinos , Gordura Subcutânea/crescimento & desenvolvimento , Gordura Subcutânea/metabolismo
12.
Am J Clin Nutr ; 112(2): 354-363, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32453423

RESUMO

BACKGROUND: Better adherence to plant-based diets has been linked to lower risk of metabolic diseases but the effect on abdominal fat distribution and liver fat content is unclear. OBJECTIVES: We aimed to examine the association between different plant-based diet indices and measures of abdominal fat distribution and liver fat content. METHODS: In a population-based sample of 578 individuals from Northern Germany (57% male, median age 62 y), diet was assessed with a validated FFQ and an overall, a healthy, and an unhealthy plant-based diet index were derived. Participants underwent MRI to assess volumes of visceral and subcutaneous abdominal adipose tissue and liver signal intensity (LSI), a measure of liver fat content. Fatty liver disease (FLD) was defined as log LSI ≥3.0. Cross-sectional associations of the plant-based diet indices with visceral and subcutaneous abdominal fat volumes, LSI, and FLD were assessed in linear and logistic regression analyses. The most comprehensive model adjusted for age, sex, education, smoking, alcohol, physical activity, energy intake, diabetes, hyperlipidemia, and BMI. RESULTS: Higher overall and healthy plant-based diet indices both revealed statistically significant associations with lower visceral and subcutaneous abdominal adipose tissue volumes and with lower odds of FLD in multivariable-adjusted models without BMI. Upon additional adjustment for BMI, only the association of the healthy plant-based diet with visceral adipose tissue remained statistically significant (per 10-point higher healthy plant-based diet index, percentage change in visceral adipose tissue: -4.9%, 95% CI: -8.6%, -2.0%). None of the plant-based diet indices was associated with LSI. The unhealthy plant-based diet index was unrelated to any of the abdominal or liver fat parameters. CONCLUSIONS: Adherence to healthy plant-based diets was associated with lower visceral adipose tissue. None of the other examined associations remained statistically significant after adjustment for BMI.


Assuntos
Dieta Vegetariana , Gorduras/metabolismo , Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Verduras/metabolismo , Idoso , Índice de Massa Corporal , Estudos Transversais , Dieta Saudável , Ingestão de Energia , Exercício Físico , Comportamento Alimentar , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Verduras/química
13.
Clin Sci (Lond) ; 134(10): 1167-1180, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32458968

RESUMO

In the present study, we evaluated the metabolic effects of green tea polyphenols (GTPs) in high-fat diet (HFD) fed Zucker fatty (ZF) rats, in particular the effects of GTP on skeletal muscle insulin sensitivity. Body weight, visceral fat, glucose tolerance, lipid profiles and whole-body insulin sensitivity were measured in HFD-fed ZF rats after 8-week-treatment with GTP (200 mg/kg of body weight) or saline (5 ml/kg of body weight). Zucker lean rats were studied as controls. Ex vivo insulin-mediated muscle glucose uptake was assessed. Immunoblotting was used to evaluate the expression of key insulin signalling proteins in skeletal muscle. GTP treatment attenuated weight gain (P<0.05) and visceral fat accumulation (27.6%, P<0.05), and significantly reduced fasting serum glucose (P<0.05) and insulin (P<0.01) levels. Homoeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance, was lower (P<0.01) in GTP-treated animals compared with ZF controls. Moreover, insulin-stimulated glucose uptake by isolated soleus muscle was increased (P<0.05) in GTP-ZF rats compared with ZF-controls. GTP treatment attenuated the accumulation of ectopic lipids (triacyl- and diacyl-glycerols), enhanced the expression and translocation of glucose transporter-4, and decreased pSer612IRS-1 and increased pSer473Akt2 expression in skeletal muscle. These molecular changes were also associated with significantly decreased activation of the inhibitory (muscle-specific) protein kinase (PKC) isoform, PKC-θ. Taken together, the present study has shown that regular ingestion of GTP exerts a number of favourable metabolic and molecular effects in an established animal model of obesity and insulin resistance. The benefits of GTP are mediated in part by inhibiting PKC-θ and improving muscle insulin sensitivity.


Assuntos
Resistência à Insulina , Insulina/metabolismo , Músculo Esquelético/metabolismo , Polifenóis/farmacologia , Transdução de Sinais , Chá/química , Adiposidade/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Glucose/metabolismo , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Isoenzimas/metabolismo , Masculino , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/enzimologia , Fosforilação/efeitos dos fármacos , Proteína Quinase C/metabolismo , Transporte Proteico/efeitos dos fármacos , Ratos Zucker
14.
Nat Commun ; 11(1): 1841, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296068

RESUMO

Brain insulin action regulates eating behavior and energy fluxes throughout the body. However, numerous people are brain insulin resistant. How brain insulin responsiveness affects long-term weight and body fat composition in humans is still unknown. Here we show that high brain insulin sensitivity before lifestyle intervention associates with a more pronounced reduction in total and visceral fat during the program. High brain insulin sensitivity is also associated with less regain of fat mass during a nine year follow-up. Cross-sectionally, strong insulin responsiveness of the hypothalamus associates with less visceral fat, while subcutaneous fat is unrelated. Our results demonstrate that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution. Since visceral fat is strongly linked to diabetes, cardiovascular risk and cancer, these findings have implications beyond metabolic diseases and indicate the necessity of strategies to resolve brain insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Adiposidade/genética , Adiposidade/fisiologia , Adulto , Composição Corporal/genética , Composição Corporal/fisiologia , Encéfalo/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade
15.
PLoS One ; 15(4): e0231072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275684

RESUMO

A high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations.


Assuntos
Hipertrigliceridemia/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Idoso , Índice de Massa Corporal , Colesterol/sangue , Feminino , Homeostase/genética , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/patologia , Insulina/metabolismo , Resistência à Insulina/genética , Gordura Intra-Abdominal/patologia , Lipídeos/sangue , Pulmão/metabolismo , Pulmão/patologia , Masculino , Metaboloma/genética , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/patologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco
16.
Proc Natl Acad Sci U S A ; 117(18): 9840-9850, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32303655

RESUMO

Deregulation of mitochondrial dynamics leads to the accumulation of oxidative stress and unhealthy mitochondria; consequently, this accumulation contributes to premature aging and alterations in mitochondria linked to metabolic complications. We postulate that restrained mitochondrial ATP synthesis might alleviate age-associated disorders and extend healthspan in mammals. Herein, we prepared a previously discovered mitochondrial complex IV moderate inhibitor in drinking water and orally administered to standard-diet-fed, wild-type C57BL/6J mice every day for up to 16 mo. No manifestation of any apparent toxicity or deleterious effect on studied mouse models was observed. The impacts of an added inhibitor on a variety of mitochondrial functions were analyzed, such as respiratory activity, mitochondrial bioenergetics, and biogenesis, and a few age-associated comorbidities, including reactive oxygen species (ROS) production, glucose abnormalities, and obesity in mice. It was found that mitochondrial quality, dynamics, and oxidative metabolism were greatly improved, resulting in lean mice with a specific reduction in visceral fat plus superb energy and glucose homeostasis during their aging period compared to the control group. These results strongly suggest that a mild interference in ATP synthesis through moderation of mitochondrial activity could effectively up-regulate mitogenesis, reduce ROS production, and preserve mitochondrial integrity, thereby impeding the onset of metabolic syndrome. We conclude that this inhibitory intervention in mitochondrial respiration rectified the age-related physiological breakdown in mice by protecting mitochondrial function and markedly mitigated certain undesired primary outcomes of metabolic syndrome, such as obesity and type 2 diabetes. This intervention warrants further research on the treatment of metabolic syndrome of aging in humans.


Assuntos
Envelhecimento/genética , Síndrome Metabólica/metabolismo , Mitocôndrias/genética , Estresse Oxidativo/genética , Trifosfato de Adenosina/biossíntese , Trifosfato de Adenosina/genética , Envelhecimento/metabolismo , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético/genética , Glucose/metabolismo , Envelhecimento Saudável/genética , Humanos , Gordura Intra-Abdominal/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Biogênese de Organelas , Espécies Reativas de Oxigênio/metabolismo
17.
Am J Physiol Endocrinol Metab ; 318(6): E839-E847, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32286882

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise (n = 15), or conventional lifestyle advice (n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.


Assuntos
Apolipoproteína A-I/metabolismo , HDL-Colesterol/metabolismo , Exercício Físico , Gordura Intra-Abdominal/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Triglicerídeos/metabolismo , Adulto , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Cinética , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/terapia , Resultado do Tratamento , Perda de Peso
18.
Am J Physiol Endocrinol Metab ; 318(6): E995-E1003, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315213

RESUMO

Glucocorticoids (GCs) play critical roles in adipose tissue metabolism. Here, we compare in a mouse model the effects of chronic glucocorticoid excess and diet-induced obesity on white adipose tissue mass and distribution, by focusing on visceral adipose tissue (VAT) fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a noninvasive mouse model of hypercortisolism to compare GC-induced effects on adipose tissue with diet-induced obesity [high-fat diet (HFD) 45%] and control mice after 10 wk of treatment. Subcutaneous adipose tissue (SAT) and VAT mass and distribution were measured by nuclear magnetic resonance imaging (NMRI). Fatty acid composition in VAT was analyzed by NMR spectroscopy and gas chromatography. Gene expression of key enzymes involved in DNL was analyzed in liver and VAT. Macrophage infiltration markers and proinflammatory cytokines were measured by gene expression in VAT. HFD or GC treatment induced similar fat mass expansion with comparable distribution between SAT and VAT depots. However, in VAT, GCs induce DNL, higher palmitic acid (PA), macrophage infiltration, and proinflammatory cytokine levels, accompanied by systemic nonesterified fatty acid (NEFA) elevation, hyperinsulinemia, and higher homeostatic model assessment for insulin resistance (HOMA-IR) levels compared with diet-induced obesity. Thus, chronic hypercortisolism induces DNL and fatty acid composition changes toward increased SFA and reduced polyunsaturated fatty acid (PUFA) levels in VAT, promoting macrophage recruitment and proinflammatory cytokines, suggesting a worse cardiometabolic profile even compared with HFD mice.


Assuntos
Síndrome de Cushing/metabolismo , Citocinas/imunologia , Ácidos Graxos não Esterificados/metabolismo , Ácidos Graxos Insaturados/metabolismo , Inflamação/imunologia , Gordura Intra-Abdominal/metabolismo , Lipogênese , Macrófagos/imunologia , Animais , Corticosterona/farmacologia , Síndrome de Cushing/imunologia , Citocinas/efeitos dos fármacos , Dieta Hiperlipídica , Ácidos Graxos/metabolismo , Insulina/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/imunologia , Macrófagos/efeitos dos fármacos , Imagem por Ressonância Magnética , Camundongos , Obesidade/imunologia , Obesidade/metabolismo , Ácido Palmítico/metabolismo
20.
PLoS One ; 15(4): e0230885, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240221

RESUMO

Regulatory T cells (Treg) play essential roles in maintaining immune homeostasis. Resident Treg in visceral adipose tissue (VAT-Treg) decrease in male obese mice, which leads to the development of obesity-associated chronic inflammations and insulin resistance. Although gender differences in immune responses have been reported, the effects of the difference in metabolic environment on VAT-Treg are unclear. We investigated the localization of VAT-Treg in female mice in comparison with that in male mice. On a high-fat diet (HFD), VAT-Treg decreased in male mice but increased in female mice. The increase was abolished in ovariectomized and HFD-fed mice, but was restored by estrogen supplementation. The IL33 receptor ST2, which is important for the localization and maturation of VAT-Treg in males, was reduced in CD4+CD25+ T cells isolated from gonadal fat of obese mice of both genders, suggesting that a different system exists for VAT-Treg localization in females. Extensive analysis of chemokine expression in gonadal fat and adipose CD4+CD25+T cells revealed several chemokine signals related to female-specific VAT-Treg accumulation such as CCL24, CCR6, and CXCR3. Taken together, the current study demonstrated sexual dimorphism in VAT-Treg localization in obese mice. Estrogen may attenuate obesity-associated chronic inflammation partly through altering chemokine-related VAT-Treg localization in females.


Assuntos
Estrogênios/metabolismo , Obesidade/imunologia , Linfócitos T Reguladores/metabolismo , Tecido Adiposo/metabolismo , Adiposidade , Animais , Dieta Hiperlipídica , Estradiol/farmacologia , Estrogênios/imunologia , Feminino , Inflamação/metabolismo , Resistência à Insulina/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Gordura Intra-Abdominal/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores Sexuais , Linfócitos T Reguladores/imunologia
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