Biomedical subjects

Claude Remacle

Publications and source records attributed to Claude Remacle.

12 recordsLinked to original sources

PubMed2006

The regulation of IGFs and IGFBPs by prolactin in primary culture of fetal rat hepatocytes is influenced by maternal malnutrition.

During perinatal development, the regulation of IGF system appears to be growth hormone (GH) independent. By using highly purified primary fetal hepatocytes, we investigated the role of prolactin (PRL) in the regulation of IGF system and hepatocyte proliferation. We also analyzed the consequence of a maternal low-protein (LP) diet on the regulation of IGF, IGF-binding protein (IGFBP), and hepatocyte proliferation by prolactin. Pregnant Wistar rats were fed a control (C) diet (20% protein) or isocaloric (LP; 8%) diet throughout gestation. On day 21.5, fetal hepatocytes were cultured for 4 days and incubated with rat prolactin. In the C hepatocytes, PRL at 100 ng/ml decreased the abundance of IGFBP-1 and IGFBP-2 by 50 (P < 0.05) and 60% (P < 0.01), respectively. It also reduced by 70% the level of IGF-II mRNA (P < 0.01). By contrast, PRL failed to modulate IGFBP-1 and IGFBP-2 production by LP hepatocytes, and this was associated with reduced abundance of the short form of PRL receptor (P < 0.05). PRL had no effect on either the proliferation or the IGF-I production by C and LP hepatocytes, although it reduced the expression of IGF-II. These results suggest that prolactin influences hepatocyte proliferation in vitro by inhibiting IGFBP-1, IGFBP-2, and IGF-II levels, which may coincide with the decline of IGF-II observed in rodents during late gestation in vivo. On the other hand, maternal LP diet induces a resistance of fetal hepatocytes to PRL.

Animals↗

PubMed2006

Fibrinolysis and cardiovascular risk factors: association with fibrinogen, lipids, and monocyte count.

BACKGROUND: Numerous risk factors for cardiovascular disease (CVD) have been determined by clinical epidemiological observations. The missing link could be related to endothelial dysfunction and the resulting hypofibrinolysis. METHODS: In this cross-sectional study, we evaluated 160 subjects (134 in primary prevention) characterized by their clinical cardiovascular risk factors (CVRF), i.e., age, gender, diabetes, hypertension, smoking habit, and history of coronary event or stroke, and by their blood parameters, i.e., C-reactive protein (CRP), fibrinogen, leukocyte count (WBC), monocyte count (MC), total cholesterol, HDL cholesterol (HDL-c), LDL cholesterol (LDL-c), and triglycerides. We assessed their fibrinolytic capacity with a new method, Euglobulin Clot Lysis Time (ECLT). The effects of these clinical and biological parameters were evaluated in multivariate analysis (backward stepwise regression). RESULTS: ECLT was correlated with the Framingham risk score and was significantly influenced by the number of clinical CVRF. MC was confirmed to be an important predictive factor influencing ECLT. In subjects without clinical CVRF (n=46), 67% of the variability of ECLT was explained by a combination of MC, LDL-c, and fibrinogen. CONCLUSION: ECLT is related to the number of epidemiologically defined clinical CVRF and to MC. Because it integrates many risk factors, we suggest that fibrinolytic function could be a biological test useful for physicians in the cardiovascular risk assessment of their patients.

Journal Article↗

PubMed2006

Maternal protein intake in the pregnant rat programs the insulin axis and body composition in the offspring.

Evidence to support an association between early nutrition and the development of obesity in the rat is equivocal. In this study we have investigated the postnatal growth, glucose tolerance, and adipocyte function of the offspring from pregnant rats fed with diets containing either 20% or 8% protein during gestation. By 25 weeks of age, the female offspring of dams fed with the diet containing 8% protein had a significantly lower adult body weight due in part to a decrease in body fat. The peak concentration of insulin after oral administration of a glucose dose was significantly lower in both the male and female offspring of the dams fed with the diet containing 8% protein. However, the ability of insulin to stimulate lipogenesis or suppress lipolysis in fat cells isolated from the offspring was not influenced by the prenatal diet. Hepatic phosphoenolpyruvate carboxykinase activity was reduced in female offspring of dams fed with the diet containing 8% protein. These results show that adult body composition is determined during the prenatal period as a result of programming of the insulin axis. This metabolic programming influences hepatic metabolism; however, there is no evidence for a programmed change in adipocyte function.

Adipocytes↗

PubMed2006

The importance of catch-up growth after early malnutrition for the programming of obesity in male rat.

OBJECTIVE: To investigate whether catch-up growth after maternal malnutrition would favor the development of obesity in adulthood. RESEARCH METHODS AND PROCEDURES: Pregnant rats were submitted to protein or calorie restriction during the course of gestation. During lactation, pups were protein-restricted, normally fed, or overfed [reduced litter size, control (C) diet]. At weaning, rats were transferred to chow or to a hypercaloric diet (HCD) known to induce obesity. Body weight, food intake, blood parameters, glucose tolerance, adipocyte cellularity, and adipose factors contributing to cardiovascular disease development were measured. RESULTS: Protein and calorie restriction during gestation led to growth retardation at birth. If malnutrition was prolonged throughout lactation, adult body weight was permanently reduced. However, growth-retarded offspring overfed during the suckling period underwent a rapid catch-up growth and became heavier than the normally fed Cs. Offspring of calorie-restricted rats gained more weight than those of dams fed protein-restricted diet. Feeding an HCD postnatally amplified the effect of calorie restriction, and offspring that underwent catch-up growth became more obese than Cs. The HCD was associated with hyperphagia, hyperglycemia, hyperinsulinemia, glucose intolerance, insulin resistance, and adipocyte hypertrophy. The magnitude of effects varied depending on the type and the timing of early malnutrition. The expression of genes encoding factors implicated in cardiovascular disease was also modulated differently by early malnutrition and adult obesity. DISCUSSION: Catch-up growth immediately after early malnutrition should be a key point for the programming of obesity.

Adipocytes↗

PubMed2006

Is taurine a functional nutrient?

PURPOSE OF REVIEW: Taurine, a free amino acid, is found in millimolar concentrations in most mammalian tissues. Mammals are able to synthesize taurine endogenously, but some species such as humans are more dependent on dietary sources of taurine. A growing body of evidence suggests that taurine plays a preponderant role in many physiological processes, which will be summarized in this review. RECENT FINDINGS: Evidence for the requirement of taurine in the human diet has been obtained in many studies involving animal models and a few clinical trials. Recent and past studies suggested that taurine might be a pertinent candidate for use as a nutritional supplement to protect against oxidative stress, neurodegenerative diseases or atherosclerosis. Taurine has demonstrated promising actions in vitro, and as a result clinical trials have begun to investigate its effects on various diseases. SUMMARY: Taurine appears to have multiple functions and plays an important role in many physiological processes, such as osmoregulation, immunomodulation and bile salt formation. Taurine analogues/derivatives have recently been reported to have a marked activity on various disorders. Taken together, these observations actualize the old story of taurine.

Animals↗

PubMed2006

Triggering of inflammatory response by myeloperoxidase-oxidized LDL.

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-alpha by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 microg/mL and 200 microg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 microg/mL) increased the production of TNF-alpha 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.

Albumins↗

PubMed2005

Programming of the endocrine pancreas by the early nutritional environment.

A substantial body of evidence now suggests that poor intrauterine milieu elicited by maternal nutritional disturbance or placental insufficiency may programme susceptibility in the foetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. Further data showing the developmental programming of the metabolic syndrome are now available thanks to animal studies in which the foetal environment has been manipulated. This review examines the developmental programming of glucose intolerance by disturbed intrauterine metabolic condition in rats. It focuses on the alteration of the endocrine pancreas at birth. Long-term consequences, deterioration of glucose tolerance and even transgenerational effects are reported. Maternal protein, caloric restriction and diabetes during gestation/lactation lead to altered beta-cell mass. This review also tempts to identify cellular and molecular mechanisms involved in this process.

Animals↗

PubMed2005

Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats.

We have evaluated the influence of oligofructose (OFS), a fermentable dietary fibre, on glucose homeostasis, insulin production and intestinal glucagon-like peptide-1 (GLP-1) in streptozotocin-treated diabetic rats. Male Wistar rats received either i.v. streptozotocin (STZ; 40 mg/kg) or vehicle (CT); one week later, they were fed for 6 weeks with either the standard diet (STZ-CT), or with a diet containing 10% oligofructose (STZ-OFS); both diets were available ad libitum. In a second set of experiments (duration 4 weeks), a supplemental group of food-restricted rats (STZ-Res) receiving a similar intake as CT rats, was added. OFS improved glucose tolerance and reduced food intake as compared with STZ-CT rats in both the post-prandial state and after an oral glucose tolerance test. After 6 weeks, portal and pancreatic insulin concentrations were doubled in STZ-OFS rats. Food restriction improved these parameters when compared with STZ-CT rats, but to a lesser extent than in the STZ-OFS group. We have shown that OFS treatment increased portal and colonic GLP-1(7-36) amide levels and doubled colonic proglucagon and prohormone convertase 1 mRNA levels; both OFS and food restriction lowered ileal GLP-1(7-36) amide levels as compared with levels in STZ-CT rats. We propose that OFS, through its fermentation in the colon, promotes the expression and secretion of colonic peptides, namely GLP-1(7-36) amide, with beneficial consequences on glycaemia, insulin secretion and hyperphagia in diabetic rats.

Actins↗

PubMed2004

Relationship between CRP and hypofibrinolysis: Is this a possible mechanism to explain the association between CRP and outcome in critically ill patients?

BACKGROUND-: Endothelial cell dysfunction may be implicated in the development of multiple organ failure (MOF) by a number of mechanisms. Among these, altered fibrinolysis promotes fibrin deposition, which may create microvascular alterations during inflammation. Elevated concentrations of C-reactive protein (CRP), especially when these persist over time, are correlated with an increased risk of MOF and death. CRP may inhibit fibrinolysis by inducing plasminogen activator inhibitor-1 (PAI-1) release from human aortic endothelial cells. Moreover, the administration of recombinant CRP in volunteers may increase circulating PAI-1 levels.In this study, we tested the hypothesis that CRP is associated with hypofibrinolysis in intensive care patients with and without sepsis. METHODS-: We studied the association of inflammation and abnormal fibrinolysis in intensive care unit (ICU) patients with (n = 11) and without (n = 21) sepsis. The inflammatory response was assessed by serum concentration of C-reactive protein (CRP), a marker of the acute phase reaction, which increase rapidly in the inflammatory response, and the plasma fibrinolytic capacity was evaluated by the Euglobulin Clot Lysis Time (ECLT), determined by a new semi-automatic method. RESULTS-: ECLT was significantly higher in septic than non-septic patients (1104 +/- 439 vs 665 +/- 275 min; p = 0.002) and was significantly correlated with CRP concentration (R2 = 0.45; p < 0.001). In a multivariate analysis, CRP was the strongest predictor of ECLT (R2 = 0.51, F = 25.6, p < 0.001). In addition, the overall ICU length of stay was significantly correlated with CRP (R2 = 0.264, p = 0.003) and ECLT (R2 = 0.259, p = 0.003). CONCLUSION-: In critically ill patients a significant correlation thus exists between plasma fibrinolytic capacity and serum CRP levels. Our data were obtained in the first 24 hours of ICU admission or of sepsis, thus, the relation between CRP and hypofibrinolysis appeared very quickly. This finding is compatible with a link between inflammation and abnormal fibrinolysis, and may explain the negative prognostic value of CRP in critically ill patients.

Journal Article↗

PubMed2004

Prenatal protein restriction does not affect the proliferation and differentiation of rat preadipocytes.

Poor development in utero may favor the development of obesity in adulthood. Animal studies showed that embryo manipulation in vitro or nutritional insults during the embryonic and fetal stages of development may lead to obesity in adult life. We studied the in vitro proliferation and differentiation of adipocytes to investigate whether early protein restriction may program cell growth and development. In a series of experiments, 2 different low-protein diet protocols were compared. In both cases, pregnant rats were fed a diet with a high (18-20%) or low (8-9%) protein content during gestation and/or lactation. Preadipocytes were isolated from the fetuses, neonates, and weanling offspring. Moderate protein restriction, imposed during either gestation and/or lactation, did not affect the capacity of preadipose cells to divide or store fat. Because previous studies showed that early protein restriction alters the metabolism of sulfur amino acids, we also investigated the effects of methionine, taurine, and homocysteine on proliferation and differentiation of preadipocytes. The supplementation of the diet with methionine or the addition of homocysteine and taurine to the culture media did not influence the development of preadipocytes. We obtained no evidence for the direct reprogramming of the precursor or stem cells and suggest that the subsequent alteration in fat accretion may therefore reflect a change in the neuroendocrine environment.

Adipocytes↗

PubMed2003

Isocaloric maternal low-protein diet alters IGF-I, IGFBPs, and hepatocyte proliferation in the fetal rat.

We investigated the effect of an isocaloric maternal low-protein diet during pregnancy in rats on the proliferative capacity of cultured fetal hepatocytes. The potential roles of these changes on the IGF-IGF-binding protein (IGFBP) axis, and the role of insulin and glucocorticoids in liver growth retardation, were also evaluated. Pregnant Wistar rats were fed a control (C) diet (20% protein) or a low-protein (LP) diet (8%) throughout gestation. In primary culture, the DNA synthesis of hepatocytes derived from LP fetuses was decreased by approximately 30% compared with control hepatocytes (P < 0.05). In parallel, in vivo moderate protein restriction in the dam reduced the fetal liver weight and IGF-I level in fetal plasma (P < 0.01) and augmented the abundance of 29- to 32-kDa IGFBPs in fetal plasma (P < 0.01) and fetal liver (P < 0.01). By contrast, the abundance of IGF-II mRNA in liver of LP fetuses was unaffected by the LP diet. In vitro, the LP-derived hepatocytes produced less IGF-I (P < 0.01) and more 29- to 32-kDa IGFBPs (P < 0.01) than hepatocytes derived from control fetuses. These alterations still appeared after 3-4 days of culture, indicating some persistence in programming. Dexamethasone treatment of control-derived hepatocytes decreased cell proliferation (54 +/- 2.3%, P < 0.01) and stimulated 29- to 32-kDa IGFBPs, whereas insulin promoted fetal hepatocyte growth (127 +/- 5.5%, P < 0.01) and inhibited 29- to 32-kDa IGFBPs. These results show that liver growth and cell proliferation in association with IGF-I and IGFBP levels are affected in utero by fetal undernutrition. It also suggests that glucocorticoids and insulin may modulate these effects.

Animals↗

PubMed2003

Taurine supplementation of a low protein diet fed to rat dams normalizes the vascularization of the fetal endocrine pancreas.

In rats, an isoenergetic low protein diet (LP) given throughout gestation perturbs the development of the endocrine pancreas by reducing beta-cell mass and islet vascularization at birth. Taurine, an important amino acid during development, has been found to be low in fetal and maternal plasma. When added to a LP diet, taurine normalizes beta-cell mass. Therefore, we investigated the ability of taurine to correct altered islet vascularization. Rats were given 20% [control (C)] or 8% (LP) protein in the diet with or without supplementation with 25 g/L taurine (T) in drinking water (C+T and LP+T) during gestation and lactation. Immunostaining for vascular endothelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1), a VEGF receptor, was performed on fetal and neonatal pancreatic sections. Blood vessel density and blood vessel number were analyzed morphometrically on semi-thin sections. Taurine supplementation restored a normal volume and numerical density of vessels in fetal islets. The number of cells showing immunoreactivity for VEGF and Flk-1 was reduced by 33 and 45%, respectively, in islet cells from LP fetuses. In 1-mo-old pups, VEGF-positive cells remained decreased by nearly 22%. Both VEGF and Flk-1 were restored in pancreatic endocrine cells of fetuses and pups given taurine. The LP diet induced a threefold overexpression of Flk-1 in ductal cells, which contain precursors of beta cells. However, taurine supplementation was without effect. In conclusion, underexpression of VEGF and Flk-1 is associated with the lower fetal islet vascularization induced by the maternal malnutrition. The addition of taurine to the maternal diet prevents such damage and has a potential role in islet vasculogenesis.

Animals↗