RESUMEN
PURPOSE: Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. METHODS: Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). RESULTS: At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1ß or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. CONCLUSION: MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.
Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Suplementos Dietéticos , Regulación de la Expresión Génica , Grasa Intraabdominal/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Obesidad/dietoterapia , Taurina/uso terapéutico , Adiposidad , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Biomarcadores/sangre , Biomarcadores/metabolismo , Hiperinsulinismo/dietoterapia , Hiperinsulinismo/etiología , Hiperinsulinismo/inmunología , Hiperinsulinismo/metabolismo , Proteínas I-kappa B/agonistas , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Inyecciones Subcutáneas , Interleucina-4/antagonistas & inhibidores , Interleucina-4/sangre , Interleucina-4/metabolismo , Grasa Intraabdominal/inmunología , Masculino , Inhibidor NF-kappaB alfa/agonistas , Inhibidor NF-kappaB alfa/genética , Obesidad/etiología , Obesidad/inmunología , Obesidad/metabolismo , Fosforilación , Procesamiento Proteico-Postraduccional , Ratas Wistar , Glutamato de Sodio/administración & dosificación , Glutamato de Sodio/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
AIMS: Fat deposition in the liver, which leads to nonalcoholic fatty liver disease is associated with obesity. Taurine (Tau) regulates lipid metabolism, representing a possible nutraceutical agent against obesity and its comorbidities. Here, we investigated whether Tau supplementation prevents hepatic lipid accumulation by regulation of the main hepatic genes involved in de novo lipogenesis and ß-oxidation. MAIN METHODS: Male rats received subcutaneous injections of monosodium glutamate (MSG; 4 mg/kg body weight/day) or saline (control group, CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5% Tau in drinking water (CTau and MTau). KEY FINDINGS: MSG-treated rats were normoglycemic, hypertriglyceridemic and insulin resistant (IR). MSG rats also exhibited massive obesity and higher hepatic triglyceride (TG) content. This effect was associated with enhanced gene expression of fatty acid synthase (FASN), but reduced carbohydrate response element-binding protein (ChREBP), microsomal TG transfer protein (MTP) and carnitine palmitoyltransferase (CPT)-1a mRNAs in MSG livers. Tau supplementation decreased whole body fat accumulation and serum TG levels, without altering IR. Tau also normalized hepatic TG content by enhancing ChREBP, MTP, peroxisome proliferator-activated receptor (PPAR)-α, ACO (acyl-CoA oxidase) and CPT-1a gene expressions. SIGNIFICANCE: Therefore, increased hepatic TG deposition in MSG-obese rats is associated with an enhanced FASN, and reduced MTP and CPT-1a genes. Tau supplementation prevented obesity and hepatic TG deposition by upregulating MTP mRNA, ameliorating hepatic lipid efflux, and consequently enhancing PPAR-α which increases lipid oxidation through ACO and CPT-1a gene expressions.
Asunto(s)
Suplementos Dietéticos , Ácidos Grasos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Obesidad/prevención & control , Taurina/farmacología , Animales , Hígado/patología , Masculino , Obesidad/metabolismo , Obesidad/patología , Ratas , Ratas WistarRESUMEN
The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.