RESUMO
The di(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental chemical with detrimental health effects. The present work was designed to asses some potential mechanisms by which DEHP causes, among others, a reduced body fat retention. Since this effect could be related to an alteration of adipocyte triacylglycerol (TG) metabolism, we evaluated the effects of dietary DEHP in adipose tissues upon (1) the number and size of fat cells; (2) the basal and stimulated lipolysis and (3) the lipoprotein lipase (LPL) activity. Groups of male Wistar rats were fed for 21 days a control diet alone (control group) or the same control diet supplemented with 2% (w/w) of DEHP (DEHP group). The LPL activity of DEHP-fed rats was increased in lumbar and epididymal adipose tissues. These rats had significantly reduced weight in epididymal and lumbar tissues, together with reduced size of epididymal adipocytes. These alterations do not seem to be associated with higher lipid mobility because neither basal lipolysis nor 'in vitro' stimulated lipolysis by noradrenaline (NA) showed to be modified by DEHP. Based on these results, we concluded that the adipose tissue size reduction induced by DEHP intake is not due to changes in lipolysis nor to a decreased LPL activity. More research is needed to achieve a comprehensive understanding of the potential mechanisms by which DEHP causes, among others, a reduced body fat retention.
Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Dietilexilftalato/toxicidade , Poluentes Ambientais/farmacologia , Lipólise/efeitos dos fármacos , Lipase Lipoproteica/metabolismo , Plastificantes/toxicidade , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo Branco/citologia , Adiposidade , Animais , Peso Corporal/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Contaminação de Alimentos , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/enzimologia , Gordura Intra-Abdominal/metabolismo , Masculino , Norepinefrina/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Triglicerídeos/metabolismoRESUMO
OBJECTIVE: Our aim was to investigate the effects of dietary conjugated linoleic acid (CLA) at high-fat (HF) levels on parameters related to triacylglycerol (TG) regulation and some potential impacts on liver damage. METHODS: Growing mice were fed a control diet (7% corn oil), an HF diet containing 20% corn oil, or an HF diet containing 3% CLA (HF + CLA) for 30 d. Tissue and organ weights, plasma and tissue TG levels, and parameters related to their regulation were evaluated. Liver oxidative status was also assessed. RESULTS: Dietary CLA showed detrimental and beneficial effects. CLA added to the HF diet caused hepatomegaly (+32%) and exacerbated the hepatic TG accumulation (+168%) observed with the HF diet without inducing liver damage; however, it significantly reduced plasma TG concentrations (-37%) and normalized muscular TG content. An increase in glutathione was associated with total normalization of liver lipid peroxidation. In addition, HF + CLA caused dystrophy of epididymal fat pads, even when the HF diet had increased the adipose tissue mass (30%). The biochemical mechanisms involved in the regulation of lipid levels were related to reduced (-20%) hepatic very low-density lipoprotein-TG secretion and decreased muscle (-35%) and adipose (-49%) tissue contributions to the removal of plasma TG by lipoprotein lipase enzymes. CONCLUSION: Examination of CLA at HF levels showed hepatomegaly and exacerbation of lipid accretion as a negative impact; however, some positive aspects such as hypotriglyceridemia and protection against oxidative stress were also induced. Even the fat reduction is nutritionally important for weight control; the biochemical mechanisms whereby CLA mediates the potential effects could produce undesirable metabolic alterations.
Assuntos
Gorduras na Dieta/farmacologia , Ácidos Linoleicos Conjugados/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/fisiopatologia , Triglicerídeos/metabolismo , Tecido Adiposo/metabolismo , Animais , Colesterol/sangue , Óleo de Milho/farmacologia , Relação Dose-Resposta a Droga , Epididimo , Glutationa/metabolismo , Peroxidação de Lipídeos , Lipase Lipoproteica/metabolismo , Fígado/patologia , Masculino , Camundongos , Tamanho do Órgão , Estresse OxidativoRESUMO
The effects of chronic intake of di(2-ethylhexyl)phthalate (DEHP) on the main intermediate glycolytic metabolites in liver and gastrocnemius muscle were investigated in experimental animals. Male Wistar rats (90-100 g) were fed for 21 days either with a standard chow or the same diet supplemented with 2% (w/w) of DEHP. The DEHP-fed rats had an altered in vivo glucose tolerance associated with abnormal glucose intermediate metabolite contents in liver and skeletal muscle. In these rats, the hepatic content of glucose-6-phosphate (G-6-P), fructose-6-phosphate, pyruvate, lactate, glucose-1-phosphate and glycogen decreased. At the same time, the G-6-P content decreased while the pyruvate and lactate levels increased in skeletal muscle. These data, along with the high plasma glucose concentration and the normal lactate blood levels of this group, could indicate that DEHP-fed rats could present a deficiency in muscle glucose and lactate transport, a reduction of the flux through muscle hexokinase and hepatic glucokinase, and a reduction in glycogen synth-
