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 synthesis.

No abstract

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.

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.

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.