RESUMO
S-resistin, a non-secretable resistin isoform, acts as an intracrine factor that regulates adipocyte maduration, inflammatory and insulin response in 3T3-L1 cells. However, its intracellular function in vivo is still unknown. In this study, we analyze the central role of s-resistin, decreasing its hypothalamic expression using an intracerebroventricular injection of lentiviral RNAi. The data present herein support an improvement in the hypothalamic leptin and insulin signaling pathway upon s-resistin downregulation. Furthermore, hypothalamic levels of pro-inflammatory markers decrease, meanwhile those of the anti-inflammatory cytokine IL-10 increases. Interestingly, peripheral NEFA decreases alike circulating leptin and resistin levels. These data demonstrate that hypothalamic s-resistin controls fuel mobilization and adipokines secretion. Importantly, central s-resistin downregulation improves systemic insulin sensitivity, as demonstrated after an IPGTT. Interestingly, our data also indicate that s-resistin downregulation could improve hypothalamic inflammation in aged Wistar rats. Altogether, our findings suggest that hypothalamic s-resistin seems to be a key regulator of the brain-fat axis which links inflammation with metabolic homeostasis.
Assuntos
Adipócitos/metabolismo , Hipotálamo/metabolismo , Inflamação/prevenção & controle , Resistência à Insulina , Insulina/metabolismo , Resistina/antagonistas & inibidores , Adipócitos/imunologia , Adipócitos/patologia , Animais , Citocinas/metabolismo , Células HEK293 , Células HeLa , Homeostase , Humanos , Hipotálamo/imunologia , Hipotálamo/patologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , RNA Interferente Pequeno/genética , Ratos , Ratos Wistar , Resistina/genética , Resistina/metabolismoRESUMO
Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. Pomegranate is a rich source of compounds used to treat metabolic diseases including type 2 diabetes. In this study, we found that consumption of pomegranate fruit extract (PFE) predominantly reduced the serum resistin levels in ovariectomized mice, an animal model with elevated resistin levels in serum and upregulated resistin mRNA expression in white adipose tissue. Moreover, the PFE significantly reduced the secretion and intracellular protein levels of resistin in differentiated murine 3T3-L1 adipocytes, but it did not alter resistin mRNA expression. When de novo protein synthesis was inhibited by the protein synthesis inhibitor cycloheximide, the intracellular resistin protein levels were drastically reduced by the PFE, suggesting that the PFE promoted the degradation of resistin at the protein level. We also found that ellagic acid (EA), a main component of pomegranate, had the same effects on the secretion and intracellular protein level of resistin. These results suggest that EA in pomegranate suppresses resistin secretion by a novel mechanism involving the degradation of intracellular resistin protein in adipocytes.
Assuntos
Adipócitos/efeitos dos fármacos , Ácido Elágico/farmacologia , Lythraceae/química , Resistina/antagonistas & inibidores , Resistina/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Cicloeximida/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos , Extratos Vegetais/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologiaRESUMO
Recent data reported that chitosan reduces high-fat (HF) diet-induced obesity in mice without describing the metabolic consequences of such an effect. The aim of this study was to investigate the capacity of chitosan derived from edible mushrooms to modify adipocytokine levels and to assess the relevance of this effect on the development of fat mass, and on glucose and lipid metabolism in obese mice. Mice were fed a HF diet or a HF diet supplemented with 5% fungal chitosan for ten weeks. HF-induced hypertriglyceridaemia, fasting hyperinsulinaemia and fat accumulation in liver, muscle and white adipose tissue (WAT) were reduced after chitosan treatment. The higher lipid content in the caecum following treatment with chitosan suggested that this dietary fiber reduced lipid absorption. We postulated that the lower triglyceridaemia observed upon chitosan treatment could also be the result of the lower FIAF (fasting-induced adipose factor) expression observed in visceral adipose tissue. IL-6, resistin and leptin levels decreased in the serum after chitosan supplementation. We conclude that fungal chitosan counteracts some inflammatory disorders and metabolic alterations occurring in diet-induced obese mice since it decreases feed efficiency, fat mass, adipocytokine secretion and ectopic fat deposition in the liver and the muscle.