BPA, an energy balance disruptor.

Bisphenol A (BPA) is used extensively in the world and is present in a diverse range of manufactured articles including dental resins, polycarbonate plastics, and the inner coating of food cans. It is a high volume chemical, with global production at 3.6 × 10(9) kg per year. BPA was identified as a high priority for assessment of human health risk because it was considered to present greatest potential for human exposure. Most studies of the health effects of BPA have focused on endocrine disruption leading to reproductive toxicity, but it displays additional side effects, including liver damage, disrupted pancreatic ß-cell function, thyroid hormone disruption, and obesity-promoting effects. In this article, we reviewed specifically on the effects of BPA in energy balance.

Role of CD36 in oral and postoral sensing of lipids.

Obesity and associated plethora of diseases constitute a major public health challenge worldwide. The conjunction of profound changes in our lifestyle and a thrifty genetic that evolved in an environment of food scarcity largely explains this epidemic situation. Food abundance promotes our specific appetite for the more palatable food generally rich in lipids. It is noteworthy that this attraction for fatty food is not specific to humans. Rats and mice also spontaneously prefer lipid-rich food in a free-choice situation. Detection of lipids in food requires the presence of specific sensors located in strategic places (e.g., oral cavity, small intestine, brain) whose activation results in a modulation of the eating behavior. Recent data strongly suggest that the glycoprotein CD36 plays a significant role in this sensing system.

[Preliminary evaluation of the insecticide susceptibility in Anopheles gambiae and Culex quinquefasciatus from Lobito (Angola), using WHO standard assay]. / Premiers tests OMS d'évaluation de la sensibilité aux insecticides chez Anopheles gambiae et Culex quinquefasciatus à Lobito, Angola.

Field collections of the most common urban mosquito vectors Anopheles gambiae and Culex quinquefasciatus were carried out in June 2003, March 2004 and November 2005 to gather preliminary data on the insecticide susceptibility in mosquitoes from Lobito (Angola) using the WHO standard bioassays. Bioassays were performed on F0 adults emerging from the field larval collections and on unfed adults from landing catches on volunteers. Batches of mosquitoes from three selected locations (Alto Liro, San Jao and Bela Vista) were exposed for 1 hour to several insecticides such as DDT 4%, carbosulfan 0.4%, permethrin 1%, deltamethrin 0.05% and cyfluthrin 0.15%, in order to estimate the immediate knockdown times (kdT50 and kdT95) and the mortality rate after exposure. The results revealed that mosquito susceptibility to insecticides varied depending on the insecticide, the site and the period of collection. The main local malaria vector A. gambiae (both M and S forms) was basically resistant to DDT and susceptible to all pyrethoids, regardless of the period and the site of collections. The overall mortality rate due to DDT was 73% in Alto Liro, 89% in San Jao and varied depending on the period in Bela Vista between 95% in March 2004 and 100% in November 2005. The mortality due to pyrethoids was 100% at all locations, with the kdT50 and KdT95 times ranging between 9 and 16 minutes and between 18 and 29 minutes, respectively. Concerning the C. quinquefasciatus, populations from Yard and Caponte were resistant to all insecticides tested; the mortality rate was 40% with deltamethrin and 70% with permethrin, while no lethal effect was observed with DDT or carbosulfan. In conclusion, despite its probable high resistance to DDT, the main local malaria vector A. gambiae remained fully susceptible to pyrethroids. This could forecast a good biological efficacy of the scheduled vector control interventions in Angola, based on a large-scale distribution of long-lasting, insecticide-treated nets and on the implementation of indoor residual spraying. The local vector control programme must include well-adapted IEC campaigns and full participation of the community for better management of the insecticide resistance in targeted mosquitoes and for better control of malaria vector populations.

Do we taste fat?

Sense of taste informs the body about the quality of ingested foods. Five sub-modalities allowing the perception of sweet, salty, sour, bitter, and umami stimuli are classically depicted. However, the inborn attraction of mammals for fatty foods raises the possibility of an additional orosensory modality devoted to fat perception. For a long time, dietary lipids were thought to be detected only by trigeminal (texture perception), retronasal olfactory, and post-ingestive cues. This minireview analyses recent findings showing that gustation also plays a significant role in dietary lipid perception.

The gene encoding the human ileal bile acid-binding protein (I-BABP) is regulated by peroxisome proliferator-activated receptors.

Peroxisome proliferator-activator receptors (PPAR) are involved in cholesterol homeostasis through the regulation of bile acids synthesis, composition, and reclamation. As ileal bile acid-binding protein (I-BABP) is thought to play a crucial role in the enterohepatic circulation of bile acids, we investigated whether I-BABP gene expression could also be affected by PPAR. Indeed, treatment with the PPARalpha-PPARbeta/delta agonist bezafibrate led to the up-regulation of I-BABP mRNA levels in the human intestine-derived Caco-2 cells. Cotransfections of the reporter-linked human I-BABP promoter (hI-BABP-2769/+44) together with PPAR and RXR expression vectors demonstrated that the fibrate-mediated induction of the I-BABP gene is dependent on PPARalpha or PPARbeta/delta. Using progressive 5' deletions of the hI-BABP promoter and sequence analysis, we identified a putative PPAR-binding site located at the position -198 and -186 upstream of the transcription initiation site. Electrophoretic mobility shift assays showed that the PPAR/RXR heterodimer can specifically bind to this PPRE-like motif. The deletion of the PPRE within the hI-BABP promoter abolished the PPAR-mediated transactivation in transient transfection assays. The regulation of the I-BABP promoter by PPAR appears species-specific, as the mouse I-BABP promoter, which lacks a conserved PPRE, was not responsive to exogenous PPAR expression in the presence of bezafibrate. Our findings show that the I-BABP gene may be a novel target for PPAR in humans and further emphasize the role for PPAR in the control of bile acid homeostasis.

[Impact of a new parasitologic laboratory for malaria diagnosis on diagnosis and cost of malaria in a company setting: experience from Angola]. / Impact de la création d'un laboratoire de diagnostic parasitologique du paludisme sur le diagnostic et le cout du paludisme dans une entreprise: une expérience Angolaise.

In malaria endemic areas treating every fever episode as a malaria onset would result in overdiagnosis with a margin of the error varying in function of epidemiological factors. When further compounded by overestimation related to errors in parasitologic diagnosis, clinical misdiagnosis leads to unwarranted hospitalization and inappropriate treatment. In a company setting this would mean unnecessary loss of employee work time. False positive diagnosis causes overestimation of chemoresistance, overconsumption of antimalarial drugs and underestimation of other infectious diseases. Judging from these high costs, it can be assumed that improving the reliability of parasitologic diagnosis would have a positive impact on the quality of clinical management, efficiency of antimalarial use and accuracy of epidemiological surveys. This assumption was confirmed by analysis of data following start-up of a parasitologic laboratory for malaria diagnosis in the health care clinic at Sonamet's fabrication yard in Lobito, Angola. Laboratory personnel receives expert training and audit findings demonstrate consistently reliable diagnosis. This experience underscores the need for reliable parasitologic diagnosis as a prerequisite for any large-scale malaria control program.

Obesogen effects after perinatal exposure of 4,4'-sulfonyldiphenol (Bisphenol S) in C57BL/6 mice.

Bisphenol A were removed from consumer products and replaced by chemical substitutes such as Bisphenol S (BPS). Based on their structural similarity, BPS may be obesogen like Bisphenol A in mice. Our objective was to determine the impact of BPS on lipid homeostasis in C57Bl/6 mice after perinatal and chronic exposure. Pregnant mice were exposed to BPS via the drinking water (0.2; 1.5; 50µg/kg bw/d). Treatment began at gestational day 0 and continued in offspring up to 23-weeks old. Then, offspring mice were fed with a standard or high fat diet. The body weight, food consumption, fat mass and energy expenditure were measured. A lipid load test was performed to check the postprandial triglyceridemia. Plasma parameters and mRNA gene expression in adipose tissues were also analysed. BPS induced overweight in male mice offspring fed with a HFD at the two highest doses. There was no change in food intake and energy expenditure. The overweight was correlated to the fat mass, hyperinsulinemia and hyperleptinemia. The plasma triglyceride clearance was significantly increased with BPS and tyloxapol(®) (triglyceride clearance inhibitor) reversed this phenomenon. BPS induced alteration in mRNA expression of marker genes involved in adipose tissue homeostasis: hormone sensitive lipase, PPARγ, insulin receptor, SOCS3 and adiponectin. This is the first time that BPS is described as obesogenic at low doses and after perinatal and chronic exposure in male mice. BPS potentiated the obesity induced by a HFD by inducing the lipid storage linked to faster lipid plasma clearance.

Indirect dexamethasone down-regulation of the liver fatty acid-binding protein expression in rat liver.

The effects of glucocorticoids on the regulation of the liver fatty acid-binding protein (L-FABP) were studied in vivo and in primary culture of hepatocytes in rats. No change in L-FABP cytosolic content and mRNA levels occurred after adrenalectomy. By contrast, a twofold decrease in L-FABP expression was found in dexamethasone (Dex) treated rats. In primary culture of rat hepatocytes, insulin did not modify the L-FABP mRNA levels, whereas Dex produced a significant decrease. This down-regulation was independent of specific glucocorticoid receptors, of alteration in the turnover of L-FABP mRNA and did not require a de novo protein synthesis. However, it was totally prevented when 320 microM oleic acid was added in the culture medium. These findings show that the dex-mediated down-regulation of the L-FABP expression found in vivo is not due to a direct endocrine effect, but is likely secondary to changes in cellular lipid metabolism.

Output of liver fatty acid-binding protein (L-FABP) in bile.

Liver fatty acid-binding protein (L-FABP) is a small cytoplasmic molecule highly expressed in the liver. Since L-FABP exhibits affinities for several biliary components, its presence in bile was explored by Western blotting and competitive ELISA in various mammalian species. A L-FABP-like immunoreactivity was consistently found in both hepatic and gallbladder bile. A close molecular identity between this 14 kDa biliary protein and the purified L-FABP was assessed by immunological analyses and high performance capillary electrophoresis. Pharmacological induction of hepatic L-FABP biosynthesis led to a similar increase in biliary L-FABP levels showing a close relationships between the cytosolic and biliary contents of this protein. Finally, a correlation between the presence of L-FABP in bile and both bile flow and bile acid release was found. These data suggest an output of L-FABP in bile in normal conditions which might be coupled with the physiological release of biliary components.

Expression of fatty acid binding protein in the liver during pregnancy and lactation in the rat.

Expression of the liver fatty acid binding protein (L-FABP) has been studied in the liver of pregnant and lactating rats. The L-FABP concentration found in the cytosol by immuno-enzymatic assay (ELISA) was consistently higher in the dams during the pregnancy and the lactation than in the age-matched virgin females. Paradoxically, a decrease in the L-FABP mRNA level occurred in the maternal liver during the last days of the gestation. This level remained low on days 7 and 14 of the lactation. Since the transcription rate of the L-FABP gene was unchanged in the maternal liver, these data suggest a post-transcriptional regulation of the L-FABP during pregnancy and lactation in the rat. The nutritional adaptations occurring during pregnancy and lactation are not involved in this regulation since a chronic maternal food-restriction failed to correct these modifications. The mechanism of this regulation is presently unknown, but possibilities include hormonally mediated effects.

Development of conjugated linoleic acid (CLA)-mediated lipoatrophic syndrome in the mouse.

Conjugated linoleic acids (CLA) are positional and geometric dienoic isomers of linoleic acid. Dietary CLA supplementation leads to a drop in fat mass in various species, including in humans. The t10,c12-CLA isomer is responsible for this anti-obesity effect. The reduction of fat mass is especially dramatic in the mouse, in which it is associated with severe hyperinsulinemia, insulin resistance and massive liver steatosis. The origin of these adverse side effects and putative chronology of events leading to CLA-mediated lipoatrophic syndrome are presented and discussed in this review.

Ontogenesis of calcitonin mRNA in the rabbit.

Since plasma calcium levels are higher in the fetus than in the mother at the end of gestation, it has been suggested that calcitonin (CT) biosynthesis would be very active in the fetus. This hypothesis was tested in rabbit fetuses and newborns by measuring the amount of CT mRNAs found in the thyroid glands and the thyroidal CT stores. Dot-blot and Northern hybridizations with a specific CT cDNA probe (a BglII-NsiI fragment of the human CT cDNA) were used to determine the CT mRNA level. In fetuses, newborns, and mothers, only one molecular species of mRNA around 1 kb was detected by Northern hybridization with the specific CT cDNA probe. By dot-blot, CT mRNAs could be detected at 20 days of gestation on pooled fetal thyroid glands as a weak positive signal. The amount of CT mRNAs increased on day 24; at this stage they were also observed by Northern hybridization. During the last 6 days of gestation a 3-fold increase in CT mRNAs occurred in rabbit fetuses; concomitantly a 5-fold rise in the total thyroidal CT content was observed. Fetal plasma concentrations of both CT and calcium increased slightly between 24 and 30 days of gestation. After birth, the CT mRNA level was 10-fold increased between 2 and 30 days; these changes were not reflected in the plasma CT level but were probably accounted for by a rise in the number of C cells of the thyroid gland.

C cell activity during the prenatal and postnatal periods in the rat.

The high plasma calcitonin (CT) level found in suckling newborns and baby rats led us to hypothesize that thyroid C cells might be exhausted during the postnatal period. This prompted us to evaluate the CT concentration of the thyroid C cells during the prenatal and postnatal periods in the rat as the CT content to number ratio of C cells. The CT content of the thyroid gland increased exponentially from 17.5 (0.03 ng) to 21.5 (1.72 ng) days of gestation in the rat fetus; C cells were detected by immunofluorescence and counted from 19.5 days of gestation until term. A value of 600 + 90 C cells was obtained at 19.5 days, 1557 +/- 239 at 20.5 days, and 2602 +/- 536 at 21.5 days of gestation. Plasma CT concentrations were undetectable (less than 150 pg/ml) before 20.5 days of gestation, but increased to approximately 500 microgram/ml in 20.5- and 21.5-day-old fetuses. After birth, both the thyroid CT content and the number of C cells increased progressively. In 3-day-old suckling newborns, 4298 +/- 412 C cells were found; 9679 +/- 1114 were found 7 days after birth, and 12202 +/- 1280 were observed 15 days after birth; at the same stages, the CT contents of the thyroid gland were 6.54 +/- 0.18, 8.59 +/- 0.19, and 19.49 +/- 0.79 ng, respectively. Thus, the CT concentrations of the C cells (approximately 1.0 pg/cell) were roughly similar during the prenatal and postnatal periods in the rat. These results suggest the presence of active C cells during fetal life in the rat. They also indicate a capacity of C cells during the prenatal and postnatal periods to increase their secretion of CT while maintaining their hormone content, since the CT concentration of the C cell remains unaltered in spite of the high CT secretion in suckling rats.

Transcriptional induction of the fatty acid binding protein gene in mouse liver by bezafibrate.

The mechanism by which hypolipidemic peroxisome proliferators of the fibrate family induce the liver fatty acid binding protein in liver of rodents is unknown. In order to delineate the level at which this protein is induced, the transcriptional activity of the specific gene encoding for liver fatty acid binding protein was measured in isolated hepatocyte nuclei obtained from male Swiss mice daily force-fed during 7 days with 400 mg/kg body weight bezafibrate. This treatment induced a 4-fold increase in the liver fatty acid binding protein transcription rate. Liver fatty acid binding protein mRNA level, measured by Northern blot analysis and cytosolic content of this protein, analyzed by immunoblotting, increased concurrently. From these results we conclude that the increase in the cytosolic liver fatty acid binding protein level by bezafibrate is due to an enhancement of the transcription rate of the liver fatty acid binding protein gene. Whether the transcriptional effect is mediated by peroxisome proliferator-receptor remains to be elucidated.

Additive effects of dexamethasone and calcium on the calcitonin mRNA level in adrenalectomized rats.

Northern hybridizations were used to evaluate the effects of dexamathasone and calcium on calcitonin mRNA levels in adrenalectomized female rats. Two weeks after adrenalectomy, a 3.6-fold decrease in the calcitonin mRNA level was observed (28% vs 100% in sham-operated controls). After 5 days of dexamethasone treatment (1.5 mg/kg b. wt), a 2.6-fold rise in calcitonin mRNA occurred in adrenalectomized rats (73% vs 28%). This increment was higher when dexamethasone treated animals were injected with calcium (100% vs 73%). The effect of calcium on the calcitonin mRNA level of adrenalectomized rats treated or not with dexamethasone was similar, and additive in the former case. Our data suggest that calcium and dexamethasone elevate calcitonin mRNA by two different mechanisms.

9-cis-retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene.

The role of retinoic acids (RA) on liver fatty acid-binding protein (L-FABP) expression was investigated in the well differentiated FAO rat hepatoma cell line. 9-cis-Retinoic acid (9-cis-RA) specifically enhanced L-FABP mRNA levels in a time- and dose-dependent manner. The higher induction was found 6 h after addition of 10(-6) M 9-cis-RA in the medium. RA also enhanced further both L-FABP mRNA levels and cytosolic L-FABP protein content induced by oleic acid. The retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR), which are known to be activated, respectively, by 9-cis-RA and long chain fatty acid (LCFA), co-operated to bind specifically the peroxisome proliferator-responsive element (PPRE) found upstream of the L-FABP gene. Our result suggest that the PPAR-RXR complex is the molecular target by which 9-cis-RA and LCFA regulate the L-FABP gene.

Effect of bile on the intestinal bile-acid binding protein (I-BABP) expression. In vitro and in vivo studies.

Enterocytes actively transport bile acids from the ileal lumen to the portal blood. This physiological process greatly contributes to maintaining the bile acid homeostasis. However, little is known about the molecular mechanisms involved in this transport system. The effect of bile on gene expression of the intestinal bile-acid binding protein (I-BABP) expressed in the enterocytes was studied in vivo, using the by-pass method, and in vitro, using organ culture of ileum explants and Caco-2 cell line. The low cytosolic I-BABP concentration and I-BABP mRNA level found in diverted ileum was totally recovered when bile was added in the ileal lumen. Northern blot analysis of the ileal explants revealed a dose-dependent increase in the I-BABP mRNA in the presence of bile. In Caco-2 cells, the I-BABP transcript was dramatically increased in the presence of human bile while it was undetectable in the control cultures. These data offer the first evidence that biliary components regulate the I-BABP gene expressed in the enterocytes.

Increased level of calcitonin mRNA after 1,25-dihydroxyvitamin D3 injection in the rat.

Vitamin D metabolites are able to change plasma calcitonin (CT) levels, but nothing is known about a possible effect at the CT gene level. Here we have investigated the acute effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the CT biosynthetic activity of thyroid glands from adult rats. Plasma CT levels were significantly increased (X2) 1 and 2 h after 1,25-(OH)2D3 injection in the face of unchanged plasma calcium values. The thyroidal CT content also was unchanged. A 2-fold increase in CT mRNA level measured by dot-blot hybridization occurred 1 and 2 h after 1,25-(OH)2D3 administration. Expression of CT gene products was examined in the rabbit reticulocyte lysate cell-free translation assay. After polyacrylamide gel electrophoresis, specific immunoprecipitates were autoradiographed and quantified by integration. A single precursor of Mr approximately equal to 15 000 could be specifically immunoprecipitated with CT antisera. A 3-4-fold rise in translatable CT mRNA activity was observed 1 and 2 h after 1,25-(OH)2D3 injection. Thus, parallel changes in CT mRNA level, CT mRNA activity and plasma CT levels were observed in adult female rats after administration of 1,25-(OH)2D3. These findings demonstrate for the first time that 1,25-(OH)2D3 enhanced CT gene expression in the face of unchanged plasma calcium levels.

Regulation of gene expression by fatty acids: special reference to fatty acid-binding protein (FABP).

During the last years, the direct involvement of lipidic nutrients in the regulation of genes has been established. Fatty acids may induce or repress the transcription rate of several genes involved in both lipid and carbohydrate metabolisms. Gene up-regulation has been found in various tissues including liver, adipose tissue and small intestine. It is only triggered by saturated and unsaturated long-chain fatty acids or their CoA-derivatives. In contrast, gene down-regulation appears to be restricted to the liver. This negative effect is exerted only by polyunsaturated fatty acids. Long-chain fatty acids are able to regulate the expression of two different genes oppositely in the same cell type. The molecular mechanism of these fatty acid-mediated effects remains unclear. The involvement of members of the peroxisome proliferator-activated receptor is discussed.

Potassium administration and calcitonin mRNA level in the rat.

We have investigated the acute effects of elevated plasma potassium concentrations on the calcitonin (CT) mRNA level measured by dot-blot hybridization. Plasma CT levels were significantly increased (X2) 30 min after potassium administration (1.2 mmol, KCl/100 g body weight) in adult female rats; a trend towards increased values was observed 10 min after treatment. No change in plasma calcium concentration was induced by the elevated extracellular potassium levels. The amount of CT mRNA measured by dot-blot hybridization was statistically significantly increased 10 min and 30 min (around 47-55%) after potassium treatment. This finding was confirmed by a Northern blot analysis. It is suggested for the first time that the potassium-induced CT release is associated with a slight increase in CT mRNA level. The increased CT secretion was probably mediated through a rise in the ionized calcium concentration of the C-cell.