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1.
Nurs Clin North Am ; 56(4): 465-478, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34749888

RESUMO

As obesity continues a relentless march across the globe, researchers are beginning to unlock the complicated interplay among obesity, its ensuing inflammation, and downstream complications. It is becoming clear that obesity is a chronic, multifactorial, inflammatory disease of maladaptive adipose tissue mass involving complex links among genetics, hormonal-signaling, and the environment. Understanding the intricate pathogenesis of obesity and its sequela will go a long way to discovering better treatment options and lessen anti-obesity bias.


Assuntos
Tecido Adiposo/fisiopatologia , Regulação do Apetite , Epigenômica , Inflamação/fisiopatologia , Obesidade/fisiopatologia , Humanos
2.
Nutrients ; 13(7)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34371900

RESUMO

Excess caloric intake and body fat accumulation lead to obesity, a complex chronic disease that represents a significant public health problem due to the health-related risk factors. There is growing evidence showing that maternal obesity can program the offspring, which influences neonatal phenotype and predispose offspring to metabolic disorders such as obesity. This increased risk may also be epigenetically transmitted across generations. Thus, there is an imperative need to find effective reprogramming approaches in order to resume normal fetal development. Polyphenols are bioactive compounds found in vegetables and fruits that exert its anti-obesity effect through its powerful anti-oxidant and anti-inflammatory activities. Polyphenol supplementation has been proven to counteract the prejudicial effects of maternal obesity programming on progeny. Indeed, some polyphenols can cross the placenta and protect the fetal predisposition against obesity. The present review summarizes the effects of dietary polyphenols on obesity-induced maternal reprogramming as an offspring anti-obesity approach.


Assuntos
Tecido Adiposo/metabolismo , Fármacos Antiobesidade/administração & dosagem , Metabolismo Energético , Obesidade Materna/metabolismo , Obesidade Pediátrica/prevenção & controle , Polifenóis/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Tecido Adiposo/fisiopatologia , Adiposidade , Animais , Dieta Saudável , Epigênese Genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Obesidade Materna/genética , Obesidade Materna/fisiopatologia , Obesidade Pediátrica/genética , Obesidade Pediátrica/metabolismo , Obesidade Pediátrica/fisiopatologia , Gravidez , Fatores de Risco
3.
Nutrients ; 13(8)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34445036

RESUMO

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.


Assuntos
Anorexia Nervosa/etiologia , Anorexia Nervosa/fisiopatologia , Restrição Calórica , Sistema Cardiovascular/inervação , Corrida , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/fisiopatologia , Adiposidade , Animais , Anorexia Nervosa/diagnóstico por imagem , Anorexia Nervosa/patologia , Sistema Nervoso Autônomo/fisiopatologia , Modelos Animais de Doenças , Feminino , Hemodinâmica , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Folículo Ovariano/patologia , Ratos Wistar , Fatores de Tempo , Útero/patologia , Perda de Peso
4.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371968

RESUMO

In recent decades, the prevalence of obesity has risen dramatically worldwide among all age groups. Obesity is characterized by excess fat accumulation and chronic low-grade inflammation. The adipose tissue functions as a metabolically active endocrine organ secreting adipokines. A novel duo of adipokines, the anti-inflammatory secreted frizzled-related protein 5 (Sfrp5) and the proinflammatory wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (Wnt5a), signal via the non-canonical Wnt pathway. Recent evidence suggests that Sfpr5 and Wnt5a play a key role in the pathogenesis of obesity and its metabolic complications. This review summarizes the current knowledge on the novel regulatory system of anti-inflammatory Sfrp5 and pro-inflammatory Wnt5a, and their relation to obesity and obesity-related complications. Future studies are required to investigate the potential role of Sfrp5 and Wnt5a as biomarkers for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors. These adipokines may also serve as novel therapeutic targets for obesity-related disorders.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Obesidade/etiologia , Proteína Wnt-5a/fisiologia , Tecido Adiposo/fisiopatologia , Adolescente , Adulto , Animais , Fatores de Risco Cardiometabólico , Criança , Dieta Saudável , Humanos , Inflamação/fisiopatologia , Resistência à Insulina , Estilo de Vida , Hepatopatia Gordurosa não Alcoólica , Obesidade/fisiopatologia , Obesidade/terapia
5.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209600

RESUMO

The relation between changes in respiratory quotient (RQ) following dietary interventions and clinical parameters and body fat pools remains unknown. In this randomized controlled trial, participants with moderate abdominal obesity or/and dyslipidemia (n = 159) were randomly assigned to a Mediterranean/low carbohydrate (MED/LC, n = 80) or a low fat (LF, n = 79) isocaloric weight loss diet and completed a metabolic assessment. Changes in RQ (measured by indirect calorimeter), adipose-tissue pools (MRI), and clinical measurements were assessed at baseline and after 6 months of intervention. An elevated RQ at baseline was significantly associated with increased visceral adipose tissue, hepatic fat, higher levels of insulin and homeostatic insulin resistance. After 6 months, body weight had decreased similarly between the diet groups (-6 ± 6 kg). However, the MED/LC diet, which greatly improved metabolic health, decreased RQ significantly more than the LF diet (-0.022 ± 0.007 vs. -0.002 ± 0.008, p = 0.005). Total cholesterol and diastolic blood pressure were independently associated with RQ changes (p = 0.045). RQ was positively associated with increased superficial subcutaneous-adipose-tissue but decreased renal sinus, pancreatic, and intramuscular fats after adjusting for confounders. Fasting RQ may reflect differences in metabolic characteristics between subjects affecting their potential individual response to the diet.


Assuntos
Tecido Adiposo/fisiopatologia , Dieta Redutora/métodos , Obesidade Abdominal/dietoterapia , Troca Gasosa Pulmonar/fisiologia , Perda de Peso/fisiologia , Adulto , Calorimetria Indireta , Dieta com Restrição de Carboidratos/métodos , Dieta com Restrição de Gorduras/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/fisiopatologia , Resultado do Tratamento
6.
Clin Sci (Lond) ; 135(13): 1563-1590, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34231841

RESUMO

Despite obesity and diabetes markedly increasing the risk of developing cardiovascular diseases, the molecular and cellular mechanisms that underlie this association remain poorly characterised. In the last 20 years it has become apparent that chronic, low-grade inflammation in obese adipose tissue may contribute to the risk of developing insulin resistance and type 2 diabetes. Furthermore, increased vascular pro-inflammatory signalling is a key event in the development of cardiovascular diseases. Overnutrition exacerbates pro-inflammatory signalling in vascular and adipose tissues, with several mechanisms proposed to mediate this. In this article, we review the molecular and cellular mechanisms by which nutrients are proposed to regulate pro-inflammatory signalling in adipose and vascular tissues. In addition, we examine the potential therapeutic opportunities that these mechanisms provide for suppression of inappropriate inflammation in obesity and vascular disease.


Assuntos
Tecido Adiposo/metabolismo , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Metabolismo Energético , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Estado Nutricional , Obesidade/metabolismo , Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/imunologia , Tecido Adiposo/fisiopatologia , Animais , Anti-Inflamatórios/uso terapêutico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/imunologia , Sistema Cardiovascular/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Mediadores da Inflamação/antagonistas & inibidores , Obesidade/tratamento farmacológico , Obesidade/imunologia , Obesidade/fisiopatologia , Estresse Oxidativo , Transdução de Sinais
7.
Front Immunol ; 12: 668217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093565

RESUMO

Obesity is the largest risk factor for the development of chronic diseases in industrialized countries. Excessive fat accumulation triggers a state of chronic low-grade inflammation to the detriment of numerous organs. To address this problem, our lab has been examining the anti-inflammatory mechanisms of two human milk oligosaccharides (HMOs), lacto-N-fucopentaose III (LNFPIII) and lacto-N-neotetraose (LNnT). LNFPIII and LNnT are HMOs that differ in structure via presence/absence of an α1,3-linked fucose. We utilize LNFPIII and LNnT in conjugate form, where 10-12 molecules of LNFPIII or LNnT are conjugated to a 40 kDa dextran carrier (P3DEX/NTDEX). Previous studies from our lab have shown that LNFPIII conjugates are anti-inflammatory, act on multiple cell types, and are therapeutic in a wide range of murine inflammatory disease models. The α1,3-linked fucose residue on LNFPIII makes it difficult and more expensive to synthesize. Therefore, we asked if LNnT conjugates induced similar therapeutic effects to LNFPIII. Herein, we compare the therapeutic effects of P3DEX and NTDEX in a model of diet-induced obesity (DIO). Male C57BL/6 mice were placed on a high-fat diet for six weeks and then injected twice per week for eight weeks with 25µg of 40 kDa dextran (DEX; vehicle control), P3DEX, or NTDEX. We found that treatment with P3DEX, but not NTDEX, led to reductions in body weight, adipose tissue (AT) weights, and fasting blood glucose levels. Mice treated with P3DEX also demonstrated improvements in glucose homeostasis and insulin tolerance. Treatment with P3DEX or NTDEX also induced different profiles of serum chemokines, cytokines, adipokines, and incretin hormones, with P3DEX notably reducing circulating levels of leptin and resistin. P3DEX also reduced WAT inflammation and hepatic lipid accumulation, whereas NTDEX seemed to worsen these parameters. These results suggest that the small structural difference between P3DEX and NTDEX has significant effects on the conjugates' therapeutic abilities. Future work will focus on identifying the receptors for these conjugates and delineating the mechanisms by which P3DEX and NTDEX exert their effects.


Assuntos
Amino Açúcares/farmacologia , Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Leite Humano , Obesidade/prevenção & controle , Oligossacarídeos/farmacologia , Polissacarídeos/farmacologia , Adipocinas/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Adiposidade/efeitos dos fármacos , Amino Açúcares/síntese química , Animais , Anti-Inflamatórios/síntese química , Fármacos Antiobesidade/síntese química , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Citocinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Leite Humano/química , Estrutura Molecular , Obesidade/sangue , Obesidade/etiologia , Obesidade/fisiopatologia , Oligossacarídeos/síntese química , Polissacarídeos/síntese química , Relação Estrutura-Atividade , Ganho de Peso/efeitos dos fármacos
8.
Nutr Metab Cardiovasc Dis ; 31(9): 2547-2556, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34172321

RESUMO

AIMS: Epicardial adipose tissue has been reported to be associated with the development of cardiometabolic disease. Whether this is true for hypertension and non-dipper blood pressure remains controversial. Here, we conducted a systemic review and meta-analysis to evaluate the association between EAT and blood pressure. DATA SYNTHESIS: Pubmed, Embase, and Web of Science were searched for relevant papers. Studies reported on the difference of EAT thickness between hypertensive and normotensive patients, or those recorded odds ratio (OR) between EAT and hypertension were included. The standard mean difference (SMD) and ORs were extracted and pooled using a random-effects model respectively. We further assessed the effect of EAT on circadian rhythm of blood pressure by combining multiple-adjusted ORs for non-dipper blood pressure. Seven studies with an overall sample of 1089 patients reported the mean difference of EAT thickness between hypertensive and normotensive patients, and the hypertensive patients had higher EAT (SMD = 1.07; 95% CI: 0.66-1.48; I2 = 89.2%) compared with controls. However, the pooled association between EAT and hypertension from two studies was not significant (OR = 1.65, 95%CI 0.62-4.68; I2 = 87.5%). The summary risk effect of EAT on non-dipper blood pressure from six studies comprising1208 patients showed that each 1 mm increment of EAT was associated with a 2.55-fold risk of non-dipper blood pressure. CONCLUSION: Hypertensive patients tend to present higher EAT thickness near the right ventricular wall and increased EAT thickness might be associated with high risk of non-dipper blood pressure. Future researches are warranted to determine the causal link between EAT and hypertension and the underlying mechanism.


Assuntos
Tecido Adiposo/fisiopatologia , Adiposidade , Pressão Sanguínea , Hipertensão/fisiopatologia , Tecido Adiposo/diagnóstico por imagem , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pericárdio , Prognóstico , Medição de Risco , Fatores de Risco
9.
Sci Rep ; 11(1): 12549, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131242

RESUMO

Adipose tissue and adipokine concentrations change markedly during pregnancy, but the effects of physical activity on these changes are rarely studied. We aimed to assess physical activity levels in pregnant women of normal-weight (NW) or with obesity (OB), and to determine the relation with changes in fat mass and adipokines. In each trimester, pregnant women (136 NW, 51 OB) were interviewed about their physical activity and had their body composition, leptin, soluble leptin receptor (sOB-R) and adiponectin determined. NW reported higher activity and more aerobic exercise than OB during early pregnancy. Both groups maintained training frequency but reduced overall activity as pregnancy progressed. NW women reporting aerobic and/or resistance exercise and OB women reporting aerobic exercise had greater sOB-R increases (independent of BMI or gestational weight gain). In NW, exercise also associated with lower fat mass and leptin increases. Higher activity levels associated with lower gestational weight gain in both groups. The relationship between physical activity and adiponectin differed between NW and OB. Maternal exercise may partly mediate its beneficial effects through regulation of leptin bioavailability, by enhancing pregnancy-induced increases in sOB-R. This could be of particular importance in OB with pre-gestational hyperleptinemia and leptin resistance.


Assuntos
Exercício Físico/fisiologia , Ganho de Peso na Gestação/fisiologia , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Tecido Adiposo/fisiopatologia , Adulto , Composição Corporal/fisiologia , Feminino , Humanos , Obesidade/fisiopatologia , Obesidade/prevenção & controle , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/prevenção & controle
10.
Am J Physiol Endocrinol Metab ; 321(1): E169-E175, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34056922

RESUMO

Adipose is a key tissue regulating energy homeostasis. In states of obesity, caloric intake exceeds energy expenditure, thereby accelerating lipid accumulation with ongoing extracellular matrix (ECM) remodeling. Excess deposition of lipids and expansion of adipocytes potentially decrease ECM flexibility with local hypoxia and inflammation. Hypoxia and chronic low-grade inflammation accelerate the development of adipose tissue fibrosis and related metabolic dysfunctions. Recent research investigated that some cytokines and proteins are functional in regulating energy homeostasis, meanwhile, are potential targets to fight against adipose tissue fibrosis and insulin resistance. In this review, we focused on the regulatory mechanisms and mediators in remodeling of adipose tissue fibrosis, along with their relevance to clinical manifestations.


Assuntos
Tecido Adiposo/patologia , Metabolismo Energético/fisiologia , Adipócitos/fisiologia , Tecido Adiposo/fisiopatologia , Animais , Glicemia/metabolismo , Citocinas , Matriz Extracelular/fisiologia , Fibrose , Homeostase/fisiologia , Humanos , Inflamação , Metabolismo dos Lipídeos/fisiologia , Doenças Metabólicas/fisiopatologia , Mitocôndrias/fisiologia , Obesidade/fisiopatologia
11.
Biomed Pharmacother ; 140: 111655, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34029955

RESUMO

The underlying mechanism of electroacupuncture (EA) in relieving obesity, anti-inflammation and the interaction with metabolic pathways in obese mice has not been elaborated. The aim of this study was to investigate the regulation of EA on macrophage polarization in obesity tissue of diet-induced obesity mice. Mice were divided in 6 groups: normal control group, model group, EA-7 group, EA-14 group, EA-21 group and EA-28 group. Low-frequency EA was applied at "Tianshu (ST 25)", "Guanyuan (CV 4)", "Zusanli (ST 36)" and "Sanyinjiao (SP 6)" for 10 min. Adipose tissue was assessed with hematoxylin and eosin staining. Adipocytokines and pro-inflammatory factors expression was measured by ELISA. The protein and mRNA levels of macrophage markers were examined by immumohistochemical staining and RT-PCR, respectively. EA treatment was associated with a decrease of adipose tissue and large adipocytes, and an increase of small adipocytes. After EA treatment, the levels of Leptin, Chemerin, TNF-α, F4/80, iNOS, and CD11c decreased obviously in adipose tissue, while IL-4, IL-10 and CD206 levels increased significantly. Besides, TNF-α in spleen tissue was also downregulated, but IL-4 and IL-10 were upregulated. EA prevents weight gain through modulation inflammatory response and macrophage polarization in obese adipose tissues.


Assuntos
Inflamação/fisiopatologia , Macrófagos/fisiologia , Pontos de Acupuntura , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Biomarcadores/metabolismo , Regulação para Baixo/fisiologia , Eletroacupuntura/métodos , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Obesidade/fisiopatologia , RNA Mensageiro/metabolismo , Baço/metabolismo , Baço/fisiopatologia , Regulação para Cima/fisiologia
12.
PLoS One ; 16(5): e0251142, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33961647

RESUMO

The objective of this scoping review was to map the evidence on measurement properties of body composition tools to assess whole-body and regional fat and fat-free mass in adults with SCI, and to identify research gaps in order to set future research priorities. Electronic databases of PubMed, EMBASE and the Cochrane library were searched up to April 2020. Included studies employed assessments related to whole-body or regional fat and/or fat-free mass and provided data to quantify measurement properties that involved adults with SCI. All searches and data extractions were conducted by two independent reviewers. The scoping review was designed and conducted together with an expert panel (n = 8) that represented research, clinical, nutritional and lived SCI experience. The panel collaboratively determined the scope and design of the review and interpreted its findings. Additionally, the expert panel reached out to their professional networks to gain further stakeholder feedback via interactive practitioner surveys and workshops with people with SCI. The research gaps identified by the review, together with discussions among the expert panel including consideration of the survey and workshop feedback, informed the formulation of future research priorities. A total of 42 eligible articles were identified (1,011 males and 143 females). The only tool supported by studies showing both acceptable test-retest reliability and convergent validity was whole-body dual-energy x-ray absorptiometry (DXA). The survey/workshop participants considered the measurement burden of DXA acceptable as long as it was reliable, valid and would do no harm (e.g. radiation, skin damage). Practitioners considered cost and accessibility of DXA major barriers in applied settings. The survey/workshop participants expressed a preference towards simple tools if they could be confident in their reliability and validity. This review suggests that future research should prioritize reliability and validity studies on: (1) DXA as a surrogate 'gold standard' tool to assess whole-body composition, regional fat and fat-free mass; and (2) skinfold thickness and waist circumference as practical low-cost tools to assess regional fat mass in persons with SCI, and (3) females to explore potential sex differences of body composition assessment tools. Registration review protocol: CRD42018090187 (PROSPERO).


Assuntos
Tecido Adiposo/fisiopatologia , Composição Corporal/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Circunferência da Cintura/fisiologia , Absorciometria de Fóton , Tecido Adiposo/diagnóstico por imagem , Humanos , Pregas Cutâneas , Traumatismos da Medula Espinal/diagnóstico por imagem
13.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925217

RESUMO

Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.


Assuntos
Leptina/metabolismo , Insuficiência Renal Crônica/metabolismo , Tecido Adiposo/fisiopatologia , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Humanos , Rim/fisiopatologia , Leptina/efeitos adversos , Leptina/sangue , Masculino , Receptores para Leptina/genética , Insuficiência Renal Crônica/sangue
14.
J Am Heart Assoc ; 10(9): e019337, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33870707

RESUMO

Background There is debate whether body mass index is a good predictor of health outcomes because different tissues, namely skeletal muscle mass (SMM) and fat mass (FM), may be differentially associated with risk. We investigated the association of appendicular SMM (aSMM) and FM with fatal and nonfatal cardiovascular disease (CVD) and all-cause mortality. We compared their prognostic value to that of body mass index. Methods and Results We studied 356 590 UK Biobank participants aged 40 to 69 years with bioimpedance analysis data for whole-body FM and predicted limb muscle mass (to calculate aSMM). Associations between aSMM and FM with CVD and all-cause mortality were examined using multivariable Cox proportional hazards models. Over 3 749 501 person-years of follow-up, there were 27 784 CVD events and 15 844 all-cause deaths. In men, aSMM was positively associated with CVD incidence (hazard ratio [HR] per 1 SD 1.07; 95% CI, 1.06-1.09) and there was a curvilinear association in women. There were stronger positive associations between FM and CVD with HRs per SD of 1.20 (95% CI, 1.19-1.22) and 1.25 (95% CI, 1.23-1.27) in men and women respectively. Within FM tertiles, the associations between aSMM and CVD risk largely persisted. There were J-shaped associations between aSMM and FM with all-cause mortality in both sexes. Body mass index was modestly better at discriminating CVD risk. Conclusions FM showed a strong positive association with CVD risk. The relationship of aSMM with CVD risk differed between sexes, and potential mechanisms need further investigation. Body fat and SMM bioimpedance measurements were not superior to body mass index in predicting population-level CVD incidence or all-cause mortality.


Assuntos
Tecido Adiposo/fisiopatologia , Bancos de Espécimes Biológicos/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Músculo Esquelético/fisiopatologia , Adulto , Idoso , Índice de Massa Corporal , Causas de Morte/tendências , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Reino Unido/epidemiologia
15.
Am J Med Sci ; 361(6): 751-758, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33892918

RESUMO

INTRODUCTION: Some studies indicate an association between coronary artery disease (CAD) and osteoporosis. This case-control study examined the association between body composition and bone mineral content (BMC) and density (BMD) among patients with CAD. MATERIALS AND METHODS: A group of men (n = 73) with established CAD and age and sex matched controls (n=65) were included in the study. Data collected included socio-demographic information, disease related data (from cases), anthropometric measurements, serum vitamin D, calcium and phosphorous and body composition analysis using DEXA. Two groups were compared using independent sample t-test, Mann Whitney U-test or Chi square test. Pearson correlation and regression models were used to test the associations between body compartments. RESULTS: Among cases, the mean disease duration was 29 (range 5-192) months and 15% had triple vessel disease. Patients had higher mean total body fat mass (TBFM) (18869.7 vs 16733.0) g, p = 0.018), truncal fat mass (TRFM) (9259.1 vs 7992.5 g, p = 0.009) and fat percentage (28.6 vs 25.9%, p = 0.001) compared to controls. Median serum vitamin D level was significantly lower among patients (20.0 ng/mL) compared to controls (27.1 ng/mL) (p = 0.003). In both groups, TBFM and total body lean mass (TBLM) both showed significant positive correlations with total body BMD/BMC and regional BMDs. Of the two, TBLM emerged the best predictor of TBBMC/TBBMD. These associations were greater among patients than controls. CONCLUSIONS: TBLM appears to be the strongest predictor of TBBMD and TBBMC in patients and controls. The strength of associations was greater among patients compared to controls even after adjusting for possible confounders .


Assuntos
Tecido Adiposo/fisiopatologia , Composição Corporal/fisiologia , Densidade Óssea/fisiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Antropometria/métodos , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/diagnóstico , Osteoporose/fisiopatologia
16.
Am J Physiol Cell Physiol ; 320(6): C1000-C1012, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33788629

RESUMO

Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose of this study was to investigate the impact of T2D on the pancreatic fat depot. Pancreatic fat pads from 17 partial pancreatectomized patients (PPP) were collected, pancreatic preadipocytes isolated, and in vitro differentiated. Patients were grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD), and T2D. Transcriptome profiles of preadipocytes and adipocytes were assessed by RNAseq. Insulin sensitivity was estimated by quantifying AKT phosphorylation on Western blots. Lipogenic capacity was assessed with oil red O staining, lipolytic activity via fatty acid release. Secreted factors were measured using ELISA. Comparative transcriptome analysis of preadipocytes and adipocytes indicates defective upregulation of genes governing adipogenesis (NR1H3), lipogenesis (FASN, SCD, ELOVL6, and FADS1), and lipolysis (LIPE) during differentiation of cells from T2D-PPP. In addition, the ratio of leptin/adiponectin mRNA was higher in T2D than in NGT-PPP. Preadipocytes and adipocytes of NGT-PPP were more insulin sensitive than T2D-PPP cells in regard to AKT phosphorylation. Triglyceride accumulation was similar in NGT and T2D adipocytes. Despite a high expression of the receptors NPR1 and NPR2 in NGT and T2D adipocytes, lipolysis was stimulated by ANP 1.74-fold in NGT cells only. This stimulation was further increased by the PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole and forskolin increased lipolysis receptor independently 1.88-fold and 1.48-fold, respectively, solely in NGT cells. In conclusion, the metabolic status persistently affects differentiation and lipolysis of pancreatic adipocytes. These alterations could aggravate the development of T2D.


Assuntos
Adipócitos/fisiologia , Adipogenia/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Lipogênese/fisiologia , Lipólise/fisiologia , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Pâncreas/metabolismo , Pâncreas/fisiopatologia , Fosforilação/fisiologia , Triglicerídeos/metabolismo
17.
Biochimie ; 188: 20-34, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33689852

RESUMO

Aquaglyceroporins are a group of the aquaporin (AQP) family of transmembrane water channels. While AQPs facilitate the passage of water, small solutes, and gases across biological membranes, aquaglyceroporins allow passage of water, glycerol, urea and some other solutes. Thanks to their glycerol permeability, aquaglyceroporins are involved in energy homeostasis. This review provides an overview of what is currently known concerning the functional implication and control of aquaglyceroporins in tissues involved in energy metabolism, i.e. liver, adipose tissue and endocrine pancreas. The expression, role and (dys)regulation of aquaglyceroporins in disorders affecting energy metabolism, and the potential relevance of aquaglyceroporins as drug targets to treat the alterations of the energy balance is also addressed.


Assuntos
Aquagliceroporinas/fisiologia , Metabolismo Energético , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Aquagliceroporinas/química , Humanos , Fígado/metabolismo , Fígado/fisiopatologia , Pâncreas/metabolismo , Pâncreas/fisiopatologia
18.
Genes Dev ; 35(5-6): 307-328, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649162

RESUMO

Obesity is the most common cause of insulin resistance, and the current obesity epidemic is driving a parallel rise in the incidence of T2DM. It is now widely recognized that chronic, subacute tissue inflammation is a major etiologic component of the pathogenesis of insulin resistance and metabolic dysfunction in obesity. Here, we summarize recent advances in our understanding of immunometabolism. We discuss the characteristics of chronic inflammation in the major metabolic tissues and how obesity triggers these events, including a focus on the role of adipose tissue hypoxia and macrophage-derived exosomes. Last, we also review current and potential new therapeutic strategies based on immunomodulation.


Assuntos
Inflamação , Doenças Metabólicas/fisiopatologia , Tecido Adiposo/citologia , Tecido Adiposo/fisiopatologia , Hipóxia Celular , Doença Crônica , Exossomos/metabolismo , Humanos , Imunomodulação , Doenças Metabólicas/etiologia , Doenças Metabólicas/imunologia , Doenças Metabólicas/terapia
19.
J Biomed Sci ; 28(1): 22, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33781257

RESUMO

BACKGROUND: Obesity-related cardiovascular risk, end points, and mortality are strongly related to arterial stiffening. Current therapeutic approaches for arterial stiffening are not focused on direct targeting within the vessel. Perivascular adipose tissue (PVAT) surrounding the artery has been shown to modulate vascular function and inflammation. Peroxisome proliferator-activated receptor γ (PPARγ) activation significantly decreases arterial stiffness and inflammation in diabetic patients with coronary artery disease. Thus, we hypothesized that PPARγ activation alters the PVAT microenvironment, thereby creating a favorable environment for the attenuation of arterial stiffening in obesity. METHODS: Obese ob/ob mice were used to investigate the effect of PPARγ activation on the attenuation of arterial stiffening. Various cell types, including macrophages, fibroblasts, adipocytes, and vascular smooth muscle cells, were used to test the inhibitory effect of pioglitazone, a PPARγ agonist, on the expression of elastolytic enzymes. RESULTS: PPARγ activation by pioglitazone effectively attenuated arterial stiffening in ob/ob mice. This beneficial effect was not associated with the repartitioning of fat from or changes in the browning of the PVAT depot but was strongly related to improvement of the PVAT microenvironment, as evidenced by reduction in the expression of pro-inflammatory and pro-oxidative factors. Pioglitazone treatment attenuated obesity-induced elastin fiber fragmentation and elastolytic activity and ameliorated the obesity-induced upregulation of cathepsin S and metalloproteinase 12, predominantly in the PVAT. In vitro, pioglitazone downregulated Ctss and Mmp12 in macrophages, fibroblasts, and adipocytes-cell types residing within the adventitia and PVAT. Ultimately, several PPARγ binding sites were found in Ctss and Mmp12 in Raw 264.7 and 3T3-L1 cells, suggesting a direct regulatory mechanism by which PPARγ activation repressed the expression of Ctss and Mmp-12 in macrophages and fibroblasts. CONCLUSIONS: PPARγ activation attenuated obesity-induced arterial stiffening and reduced the inflammatory and oxidative status of PVAT. The improvement of the PVAT microenvironment further contributed to the amelioration of elastin fiber fragmentation, elastolytic activity, and upregulated expression of Ctss and Mmp12. Our data highlight the PVAT microenvironment as an important target against arterial stiffening in obesity and provide a novel strategy for the potential clinical use of PPARγ agonists as a therapeutic against arterial stiffness through modulation of PVAT function.


Assuntos
Tecido Adiposo/fisiopatologia , Hipoglicemiantes/farmacologia , Obesidade/fisiopatologia , PPAR gama/agonistas , Pioglitazona/farmacologia , Rigidez Vascular/fisiologia , Células 3T3 , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células RAW 264.7
20.
Nutrients ; 13(2)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668627

RESUMO

In the past few decades, obesity has reached pandemic proportions. Obesity is among the main risk factors for cardiovascular diseases, since chronic fat accumulation leads to dysfunction in vascular endothelium and to a precocious arterial stiffness. So far, not all the mechanisms linking adipose tissue and vascular reactivity have been explained. Recently, novel findings reported interesting pathological link between endothelial dysfunction with gut hormones and gut microbiota and energy homeostasis. These findings suggest an active role of gut secretome in regulating the mediators of vascular function, such as nitric oxide (NO) and endothelin-1 (ET-1) that need to be further investigated. Moreover, a central role of brain has been suggested as a main player in the regulation of the different factors and hormones beyond these complex mechanisms. The aim of the present review is to discuss the state of the art in this field, by focusing on the processes leading to endothelial dysfunction mediated by obesity and metabolic diseases, such as insulin resistance. The role of perivascular adipose tissue (PVAT), gut hormones, gut microbiota dysbiosis, and the CNS function in controlling satiety have been considered. Further understanding the crosstalk between these complex mechanisms will allow us to better design novel strategies for the prevention of obesity and its complications.


Assuntos
Disbiose/fisiopatologia , Endotélio Vascular/fisiopatologia , Hormônios Gastrointestinais/metabolismo , Microbioma Gastrointestinal/fisiologia , Obesidade/fisiopatologia , Tecido Adiposo/fisiopatologia , Animais , Encéfalo/fisiopatologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/fisiopatologia , Disbiose/complicações , Metabolismo Energético/fisiologia , Humanos , Obesidade/complicações , Obesidade/microbiologia , Saciação/fisiologia , Rigidez Vascular/fisiologia
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