RESUMO
This study investigated the effects of a grape pomace extract (GPE) rich in phenolic compounds on brown-like adipocyte induction and adiposity in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats fed a high-fat diet (HFD). HFD consumption for 10 weeks significantly increased epididymal white adipose tissue (eWAT) in WKY but not in SHR rats. Supplementation with GPE (300 mg/kg body weight/day) reduced adipocyte diameter and increased levels of proteins that participate in adipogenesis and angiogenesis, i.e., peroxisome-proliferator activated receptor gamma (PPARγ), vascular endothelial grow factor-A (VEGF-A) and its receptor 2 (VEGF-R2), and partially increased the uncoupling protein 1 (UCP-1) in WKY. In both strains, GPE attenuated adipose inflammation. In eWAT from SHR, GPE increased the expression of proteins involved in adipose tissue "browning," i.e., PPARγ-coactivator-1α (PGC-1α), PPARγ, PR domain containing 16 (PRDM16) and UCP-1. In primary cultures of SHR adipocytes, GPE-induced UCP-1 up-regulation was dependent on p38 and ERK activation. Accordingly, in 3T3-L1 adipocytes treated with palmitate, the addition of GPE (30 µM) activated the ß-adrenergic signaling cascade (PKA, AMPK, p38, ERK). This led to the associated up-regulation of proteins involved in mitochondrial biogenesis (PGC-1α, PPARγ, PRDM16 and UCP-1) and fatty acid oxidation (ATGL). These effects were similar to those exerted by (-)-epicatechin and quercetin, major phenolic compounds in GPE. Overall, in HFD-fed rats, supplementation with GPE promoted brown-like cell formation in eWAT and diminished adipose dysfunction. Thus, winemaking residues, rich in bioactive compounds, could be useful to mitigate the adverse effects of HFD-induced adipose dysfunction.
Assuntos
Adipócitos Bege/citologia , Tecido Adiposo Branco/citologia , Extratos Vegetais/farmacologia , Vitis/química , Células 3T3-L1 , Adipogenia , Tecido Adiposo , Tecido Adiposo Marrom/citologia , Animais , Peso Corporal , Diferenciação Celular , Dieta Hiperlipídica , Suplementos Nutricionais , Epididimo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Camundongos , Estresse Oxidativo , PPAR gama/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/biossíntese , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Aim: The present study aimed to analyze the expression of IL6, UCP1 and SIRT1 in adipose tissue (WAT and BAT) in association to clinical, metabolic and anthropometric parameters in obese humans. Methods: WAT and BAT samples from obese patients (n=27) were collected. IL6, UCP1 and SIRT1 markers were measured by qRT-PCR. The association between IL6, UCP1 and SIRT1 mRNA expression and anthropometric and clinical parameters were evaluated, using appropriate statistical tests. Results: Our results demonstrated that high levels of IL6 are associated with altered glucose levels in the WAT (p=0.01). In contrast, high levels of IL6 in the BAT were associated with decreased % fat (p=0.01) and fat weight (p=0.02) and increased mVO2 (p=0.02) and VO2 (p=0.02). For UCP1, a higher expression in the BAT was observed when compared to the WAT (p=0.0001). This gene expression was associated with lower values of BMI (p=0.03), % fat (P=0.02) and fat weight (P=0.02) and increased mVO2 (p=0.041) and VO2 (p=0.001). In the WAT, decreased levels of SIRT1 were associated with increased fat weight (p=0.02); in the BAT, associations were found for % fat (p=0.018) and mVO2 (p=0.03). Conclusion: These results reveal different characteristics in the biological actions between WAT and BAT in obese humans. Increased levels of IL6, UCP1 and SIRT1 in the BAT were associated with metabolic parameters improvements.
Assuntos
Tecido Adiposo Marrom , Tecido Adiposo Branco , Regulação da Expressão Gênica , Interleucina-6/biossíntese , Obesidade , Sirtuína 1/biossíntese , Proteína Desacopladora 1/biossíntese , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/patologiaRESUMO
Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly vascularized and innervated, and can be activated in adult humans. Brown adipocytes are responsible for performing non-shivering thermogenesis, which is exclusively mediated by uncoupling protein (UCP) -1 (a protein found in the inner mitochondrial membrane), the hallmark of BAT, responsible for the uncoupling of the proton leakage from the ATP production, therefore, generating heat (i.e. thermogenesis). Besides UCP1, other compounds are essential not only to thermogenesis, but also to the proliferation and differentiation of BAT, including peroxisome proliferator-activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-BF-1-RIZ1 homologous domain protein containing protein (PRDM) -16. The sympathetic nervous system centrally regulates thermogenesis through norepinephrine, which acts on the adrenergic receptors of BAT. This bound leads to the initialization of the many pathways that may activate thermogenesis in acute and/or chronic ways. In summary, this mini-review aims to demonstrate the latest advances in the knowledge of BAT.