Effect of the dietary exposure of rat to di(2-ethyl hexyl) phthalate on their metabolic efficiency.

The nutritional impact of di(2-ethyl hexyl) phthalate (DEHP), specifically its energy efficiency and nitrogen utilization, was studied in the experimental rat. Groups of male Wistar rats were fed over 21 days with a standard diet alone or a standard diet supplemented with 2% (w/w) DEHP. Food intake, body weight and nitrogen compounds excretion were measured daily. The composition and energetic content of the carcass were determined in animals of both dietary groups after the feeding period, as well as in a separate group on day 0. The food and energy intakes were similar in both groups, however, the efficiencies of energy and nitrogen use were significantly reduced in the DEHP-fed rat. These alterations were reflected by a reduction of 31% on carcass energy retention and a decrease of 26% on cumulative nitrogen balance, without changes in the body composition. The increase of urinary nitrogen excretion, mainly as urea compound, is the major contributing factor to the lower nitrogen retention. These results indicate that DEHP decreases energy efficiency and nitrogen utilization, leading to a pronounced reduction in body weight gain. In addition, this study provides a possible conceptual framework that could explain the metabolic changes induced by DEHP and related compounds in experimental animals.

Effects of chronic di(2-ethylhexyl) phthalate intake on the secretion and removal rate of triglyceride-rich lipoproteins in rats.

This work intends to characterize the nature of the plasma triglyceride level decrease in male Wistar rats fed with diets supplemented with 2% (w/w) di(2-ethylhexyl) phthalate (DEHP), a packaged-food chemical contaminant. After being fed for 21 days, the animals were assessed to determine plasma and liver lipids or to quantify the in vivo hepatic secretion and in vitro plasma removal of triglyceride-rich lipoproteins. The liver cholesterol and triglyceride contents in DEHP-fed rats were closely similar to those found in controls, co-existing with a decrease in plasma cholesterol (19%), phospholipid (14%) and triglyceride (36%) levels. The decrease of the plasma triglyceride pool size was not associated with a reduction in hepatic secretion of triglyceride. The total triglyceride lipase activity rose (32%) due to a remarkable increase (100%) of the extrahepatic lipoprotein lipase activity. We can conclude that extrahepatic lipoprotein lipase activity accounts for the hypotriglyceridaemic effect of DEHP through an increase of triglyceride removal rate.

A sucrose-rich diet affects triglyceride metabolism differently in pregnant and nonpregnant rats and has negative effects on fetal growth.

A sucrose-rich diet (SRD) causes hypertriglyceridemia in nonpregnant rats. To determine whether a SRD further enhances gestational hypertriglyceridemia, female rats were divided into the following two groups: 1) rats fed a SRD (63 g sucrose/100 g), and 2) rats that received the same diet except that the sucrose was replaced by an equal amount of cornstarch (CD). Half of the rats were mated and studied at d 20 of gestation. Body weight increase did not differ between virgin rats fed either diet, but the final body weight of pregnant rats fed SRD was lower than that of rats fed CD due to fewer fetuses per litter and lower fetal and placental weights. The SRD enhanced plasma glucose and insulin concentrations in virgin but not in pregnant rats; plasma triglycerides and FFA concentrations and the rate of triglyceride secretion into the plasma were higher in pregnant than in virgin rats fed SRD, but the increase in liver triglycerides due to SRD was higher in virgin rats. Both removal rate of a fat emulsion and adipose tissue lipoprotein lipase activity (LPL) were lower in virgin rats fed SRD than in those fed CD. They were lower in pregnant than in virgin rats fed CD. Placental and fetal liver triglyceride concentration and placental LPL were higher in rats fed SRD than in those fed CD. Both the increased triglyceride secretion by the liver and the decreased triglyceride removal from blood resulting in maternal hypertriglyceridemia may contribute to the negative effect of SRD on the developing fetus.

[Chronic consumption of brominated vegetable oils: their effect on liver secretion and catabolism of plasma lipoproteins]. / Ingesta crónica de aceites vegetales bromados: su acción sobre la secreción hepática y catabolismo de lipoproteínas plasmáticas.

We have previously reported that normal Wistar rats fed during 105 days with standard laboratory chow, supplemented with 0.5g of brominated vegetable oil (olive, sunflower) per 100 g of diet showed a significant increase of triglyceride and cholesterol content in both heart and liver. This was accompanied by a significant decrease of plasma lipid levels. Fluctuations in plasma triglyceride concentrations may be a result of either variations in the liver secretion rate of very low density lipoprotein-triglyceride (VLDL-TG), or changes in their removal rate by extrahepatic tissues or both. In the present work we have studied the contribution of both VLDL-TG secretion, and removal rates of plasma TG in the decrease of plasma TG levels, in rats fed during 105 days with a standard laboratory chow supplemented with 0.5 g per 100 g of brominated vegetable oil. VLDL-TG secretion was estimated by measuring the accumulation of plasma TG following the injection of TRITON WR 1339 and the removal rate of plasma TG by assaying plasma post-heparin lipolytic total (PHLA) and hepatic (H-TGL) lipase activities. In addition, the major lipid composition of plasma lipoprotein fractions were measured. Results were compared to those of a control group fed a laboratory chow diet during the same period of time. Our results show a decrease in both VLDL-TG secretion and plasma TG pool size accompanied by normal PHLA and H-TGL activities in animals fed the diet supplemented with brominated oils. However, the proportion of the major lipid components of the plasma lipoproteins fractions were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluación terapéutica de un hipoglucemiante oral: gliclazida / Therapeutic evaluation of an oral hypoglycemic agent: glyclazide

En este trabajo se evaluó durante 12 meses la eficacia terapéutica metabólica de la gliclazida sobre el equilibrio de la diabetes del adulto y su aceptabilidad clínica y biológica. Se estudiaron 19 pacientes diabéticos, no insulinodependiente que no respondieron al régimen y que habían sido tratados previamente con otro tipo de hipoglucemiante oral. Los pacientes (13 mujeres y 6 hombres)con edades comprendidas entre 39 y 80 años y antigüedad en su diabetes de 0-10 años, recibieron dosis de 80 a 320 mg/día, adaptada en cada caso en particular y asociada en todos ellos a un régimen apropiado restringido en carbohidratos. Los resultados bioquímicos mensuales indican que en todos los casos, la droga provoca una estabilidad glucémica que se prolonga a partir del primer mes de tratamiento, con descensos del 22 en el valor de la glucemia en ayunas respecto de los niveles pretratamiento, no observándose episodios de hipoglucemia en ningún caso en el transcurso del estudio. Las variaciones diarias realizadas al finalizar el estudio indican el logro de una estabilidad glucémica. Los resultados sugieren que el empleo de gliclazida, dentro de las condiciones de estudio adoptadas, produce una significativa y sostenida caída de los valores glucémicas medios durante el período de tiempo analizado

Evaluación terapéutica de un hipoglucemiante oral: gliclazida / Therapeutic evaluation of an oral hypoglycemic agent: glyclazide

En este trabajo se evaluó durante 12 meses la eficacia terapéutica metabólica de la gliclazida sobre el equilibrio de la diabetes del adulto y su aceptabilidad clínica y biológica. Se estudiaron 19 pacientes diabéticos, no insulinodependiente que no respondieron al régimen y que habían sido tratados previamente con otro tipo de hipoglucemiante oral. Los pacientes (13 mujeres y 6 hombres)con edades comprendidas entre 39 y 80 años y antig³edad en su diabetes de 0-10 años, recibieron dosis de 80 a 320 mg/día, adaptada en cada caso en particular y asociada en todos ellos a un régimen apropiado restringido en carbohidratos. Los resultados bioquímicos mensuales indican que en todos los casos, la droga provoca una estabilidad glucémica que se prolonga a partir del primer mes de tratamiento, con descensos del 22 en el valor de la glucemia en ayunas respecto de los niveles pretratamiento, no observándose episodios de hipoglucemia en ningún caso en el transcurso del estudio. Las variaciones diarias realizadas al finalizar el estudio indican el logro de una estabilidad glucémica. Los resultados sugieren que el empleo de gliclazida, dentro de las condiciones de estudio adoptadas, produce una significativa y sostenida caída de los valores glucémicas medios durante el período de tiempo analizado (AU)

Diazoxide prevents the development of hormonal and metabolic abnormalities present in rats fed a sucrose rich diet.

We have previously reported that normal Wistar rats fed an isocaloric, sucrose-rich (63%) diet (SRD) developed glucose intolerance and elevated triglyceride levels in plasma (P) as well as in heart (H) and liver (L) tissue. This metabolic state was accompanied by hyperinsulinism both in vivo and in vitro, suggesting that a state of insulin resistance has developed. In order to gather information on the role of hyperinsulinemia and glucose intolerance in the development of the above lipid metabolism abnormalities, diazoxide, a known insulin release blocking agent was administered (120 mg/kg/day) together with the diet (SRD + DZX) for 22 days. Control groups fed a standard chow (STD) or the STD plus diazoxide (STD + DZX) were included in the study. Under the present experimental design, DZX was able to prevent the development of hyperinsulinism, glucose intolerance and elevated levels of triacylglycerol in plasma, heart and liver present in animals fed on a sucrose rich diet. Our results suggest that mechanisms involved in the development of this nutritionally induced syndrome may include an interaction of hyperinsulinemia, with a direct effect of sucrose on several steps of lipid metabolism.

Effect of sucrose diet on insulin secretion in vivo and in vitro and on triglyceride storage and mobilisation of the heart of rats.

Basal heart triacylglycerol (TG) (mumole triacylglycerol/g of dry weight) (- before "in vitro" Langendorff perfusion -) was significantly higher in animals rendered chronically hypertriglyceridaemic (H) by a 63% sucrose-rich diet than in controls (C, standard diet); 28 +/- 2.6 means + SEM vs. 19.3 +/- 1.2; respectively (p less than 0.01). After 40' perfusion with Krebs-Henseleit buffer + 5.5 mM glucose, 2.5 mM Ca++, TG content fell to 14.2 +/- 0.6 in C and 14.9 +/- 1.9 in H (n.S.). Administration of 1 n mol x min-1 of glucagon (Gn) from min 20 to 40 reduced TG to 9.0 +/- 0.5 in C (p less than 0.05). In contrast no effect of Gn was observed in H (TG at min 40: 16.7 +/- 2.5). Glycogen (Gly) content (mumol/g of dry weight) after Gn perfusion fell from 30 +/- 1.9 to 17 +/- 2.1 (p less than 0.01) in C, while again no effect was recorded in H. "In vivo" plasma glucose fractional coefficient disappearance rate was lower (p less than 0.001) in H: 1.01 x 10(-2) +/- 0.09 x 10(-2) vs 2.61 x 10(-2) +/- 0.14 x 10(-2) in C, in spite of H showing hyperinsulin secretion. Hyperinsulinism was further documented by "in vitro" Iri release studies from incubated pancreas pieces. In the absence of glucose (G) from the incubation medium H produced 541 +/- 19.8 mU/mg weight Tissue/20', while C produced 91.2 +/- 12.7 (p less than 0.001). With 100 mg% G, H released 1058 +/- 259 and C 377 +/- 82.5 (p less than 0.001). It is suggested that hyperinsulin secretion plus insulin resistance may account for the above findings.

Colesterol en las fracciones lipoproteicas en mujeres obesas normolipemicas con o sin disminucion de la tolerancia glucida. / Cholesterol in lipoprotein fraction in normolipemic obese women with or without reduction of glucose tolerance

De acuerdo al indice ponderal y al resultado de la prueba de tolerancia a la glucosa, 92 mujeres normolipemicas fueron clasificadas en controles; obesas con tolerancia normal y obesas con disminucion de la tolerancia glucida. Segun las edades, se agruparon en menores (A) y mayores (B) de 40 anos. Se cuantifico el contenido de colesterol (C) en las fracciones lipoproteicas - aisladas por precipitacion con polianiones - y se realizaron los cocientes Cr/C alfa y C alfa/C beta + Cpre-beta considerados indices mas precisos del riesgo de enfermedad coronaria isquemica.Se encontro una disminucion significativa del C alfa en las obesas con disminucion de la tolerancia glucida frente a los controles. El cociente C alfa /C beta + Cpre-beta mostro un comportamiento similar y para A y B, respectivamente. La relacion Cr/C alfa incremento con una significacion p < 0.001 para ambos grupos.En los obesos con tolerancia normal solo se encontro modificacion en el cociente C alfa /C beta + Cpre-beta para A. Nuestros resultados demuestran una alteracion en la distribucion del colesterol entre los distintos grupos de pacientes obesas clasificadas como normolipemicas, particularmente acentuada en las que tienen disminucion de la tolerancia glucida

Colesterol en las fracciones lipoproteicas en mujeres obesas normolipemicas con o sin disminucion de la tolerancia glucida. / Cholesterol in lipoprotein fraction in normolipemic obese women with or without reduction of glucose tolerance

De acuerdo al indice ponderal y al resultado de la prueba de tolerancia a la glucosa, 92 mujeres normolipemicas fueron clasificadas en controles; obesas con tolerancia normal y obesas con disminucion de la tolerancia glucida. Segun las edades, se agruparon en menores (A) y mayores (B) de 40 anos. Se cuantifico el contenido de colesterol (C) en las fracciones lipoproteicas - aisladas por precipitacion con polianiones - y se realizaron los cocientes Cr/C alfa y C alfa/C beta + Cpre-beta considerados indices mas precisos del riesgo de enfermedad coronaria isquemica.Se encontro una disminucion significativa del C alfa en las obesas con disminucion de la tolerancia glucida frente a los controles. El cociente C alfa /C beta + Cpre-beta mostro un comportamiento similar y para A y B, respectivamente. La relacion Cr/C alfa incremento con una significacion p < 0.001 para ambos grupos.En los obesos con tolerancia normal solo se encontro modificacion en el cociente C alfa /C beta + Cpre-beta para A. Nuestros resultados demuestran una alteracion en la distribucion del colesterol entre los distintos grupos de pacientes obesas clasificadas como normolipemicas, particularmente acentuada en las que tienen disminucion de la tolerancia glucida