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

2003 ◽  
Vol 285 (5) ◽  
pp. E991-E1000 ◽  
Author(s):  
Ilham El Khattabi ◽  
Francine Grégoire ◽  
Claude Remacle ◽  
Brigitte Reusens

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 ∼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.

2013 ◽  
Vol 195 (1) ◽  
pp. 68-76 ◽  
Author(s):  
Wafaa S. Ramadan ◽  
Ilham Alshiraihi ◽  
Saleh Al-karim

1999 ◽  
Vol 81 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Myriam Sanchez-Gomez ◽  
Kjell Malmlöf ◽  
Wilson Mejia ◽  
Antonio Bermudez ◽  
Maria Teresa Ochoa ◽  
...  

The aim of the present study was to investigate the influence of dietary protein level on the protein anabolic effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I). Female growing rats were fed on either a high- or a low-protein diet with crude protein contents of 222 and 83 g/kg respectively. The diets contained the same amount of metabolizable energy (15·1 MJ/kg) and were given during a 14 d period. During the same time, three groups of rats (n 8) on each diet received subcutaneous infusions of either saline, recombinant human GH (rhGH) or recombinant human IGF-I (rhIGF-I). rhGH and rhIGF-I were given in doses of 360 and 500 μg/d respectively. The low-protein diet alone reduced significantly (P < 0·05) IGF-I concentrations in serum and in tissue taken from the gastrocnemius muscle as well as IGF-I mRNA from the same muscle. The responses to rhGH and rhIGF-I in terms of muscle IGF-I and its mRNA were variable. However, when rhIGF-I was infused into rats on the high-protein diet, significantly elevated levels of IGF-I in muscle tissues could be observed. This was associated with a significantly (P < 0·05) increased N balance, whereas rhGH significantly (P < 0·05) enhanced the N balance in rats on the low-protein diet. Thus, it can be concluded that the level of dietary protein ingested regulates not only the effect of IGF-I on whole-body N economy but also the regulation of IGF-I gene expression in muscles. The exact mechanism by which GH exerts its protein anabolic effect, however, remains to be elucidated.


AMB Express ◽  
2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Imtiaz Hussain Raja Abbasi ◽  
Farzana Abbasi ◽  
Mohamed E. Abd El-Hack ◽  
Ayman A. Swelum ◽  
Junhu Yao ◽  
...  

2002 ◽  
Vol 283 (3) ◽  
pp. R623-R630 ◽  
Author(s):  
Eric Bertin ◽  
Marie-Noëlle Gangnerau ◽  
Georges Bellon ◽  
Danièle Bailbé ◽  
Annick Arbelot De Vacqueur ◽  
...  

Fetal malnutrition is now proposed as a risk factor of later obesity and type II diabetes. We previously analyzed the long-term impact of reduced protein and/or energy intake strictly limited to the last week of pregnancy in Wistar rats. Three protocols of gestational malnutrition were used: 1) low-protein isocaloric diet (5 instead of 15%) with pair feeding to the mothers receiving the control diet, 2) restricted diet (50% of control diet), and 3) low protein-restricted diet (50% of low-protein diet). Only isolated protein restriction induced a long-term β-cell mass decrease. In the present study, we used the same protocols of food restriction to analyze their short-term impact (on day 21.5 of pregnancy) on β-cell mass development. A 50% β-cell mass decrease was present in the three restricted groups, but low-protein diet, either associated or not to energy restriction, increased fetal β-cell insulin content. Among all the parameters analyzed to further explain our results, we found that the fetal plasma level of taurine was lowered by low-protein diet and was the main predictor of the fetal plasma insulin level ( r = 0.63, P < 0.01). In conclusion, rat fetuses exposed to protein and/or energy restriction during the third part of pregnancy have a similar dramatic decrease in β-cell mass, and their ability to recover β-cell mass development retardation depends on the type of malnutrition used. Moreover, our results support the hypothesis that taurine might play an important role in fetal β-cell mass function.


Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 265-277 ◽  
Author(s):  
Wing Yee Kwong ◽  
Daniel J Miller ◽  
Elizabeth Ursell ◽  
Arthur E Wild ◽  
Adrian P Wilkins ◽  
...  

In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0–4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) inH19mRNA level. A significant reduction inH19(9.4%) andIgf2(10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression ofIgf2Rwas observed in relation to maternal diet. The reduction inH19mRNA expression did not correlate with an observed alteration in DNA methylation at theH19differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or femaleH19andIgf2imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affectedH19andIgf2imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Victor Dubois-Ferrière ◽  
René Rizzoli ◽  
Patrick Ammann

Low protein intake is associated with an alteration of bone microstructure and material level properties. However, it remains unknown whether these alterations of bone tissue could influence the response to repeated mechanical loading. The authors investigated thein vitroeffect of repeated loading on bone strength in humeri collected from 20 6-month-old female rats pair-fed with a control (15% casein) or an isocaloric low protein (2.5% casein) diet for 10 weeks. Bone specimens were cyclically loaded in three-point bending under load control for 2000 cycles. Humeri were then monotonically loaded to failure. The load-displacement curve of thein vitrocyclically loaded humerus was compared to the contralateral noncyclically loaded humerus and the influence of both protein diets. Material level properties were also evaluated through a nanoindentation test. Cyclic loading decreased postyield load and plastic deflection in rats fed a low protein diet, but not in those on a regular diet. Bone material level properties were altered in rats fed a low protein diet. This suggests that bone biomechanical alterations consequent to cyclic loading are more likely to occur in rats fed a low protein diet than in control animals subjected to the samein vitrocyclic loading regimen.


1989 ◽  
Vol 61 (2) ◽  
pp. 223-233 ◽  
Author(s):  
R. W. Rosebrough ◽  
J. P. McMurtry ◽  
N. C. Steele

1. Broiler chickens growing from 7 to 28 d of age were given: (1) a 210 g protein/kg control diet for the entire experimental period, (2) an intermittent feeding regimen (210 g protein/kg diet for either 1 or 2 d followed by a 1 d fast), or (3) a daily change in the dietary protein level from 120 to 300 g/kg diet. Treatment variables examined were lipogenesis and glucose production in vitro, and circulating concentrations of insulin, triiodothyronine (T3) and thyroxine (T4) to determine the effects of chronic or acute dietary treatments.2. Giving the 300 g protein/kg diet or withholding feed for 1 d decreased (P < 0.05) lipogenesis in vitro compared with controls.3. Giving the 120 g protein/kg diet or refeeding with a 210 g protein/kg diet for 1 or 2 d increased (P < 0.05) lipogenesis in vitro compared with controls. Glucose production was affected in the same manner.4. Fasting decreased (P < 0.05) plasma insulin and T3 and increased T4. Both refeeding and a low-protein diet increased T3. Refeeding increased and a low-protein diet decreased insulin.5. Chronic use (7-28 d of age) of either an alternating protein or intermittent feeding regimen caused greater responses compared with acute bouts (single cycle) of either of the regimens.


1988 ◽  
Vol 117 (3) ◽  
pp. 320-326 ◽  
Author(s):  
M. Maes ◽  
Y. Amand ◽  
L. E. Underwood ◽  
D. Maiter ◽  
J.-M. Ketelslegers

Abstract. In protein-calorie malnutrition, serum IGF-I concentrations are low despite high GH. This GH resistance might be due to a reduced number of liver GH binding sites as suggested by studies performed in fasted rats that were refed a low protein diet. To determine whether a postreceptor defect in GH action might also contribute to the GH resistance, we measured the number and the affinity constant of the liver GH binding sites and the serum IGF-I responses to injections of recombinant bGH in hypophysectomized female rats, fed a standard (15% protein) diet (N = 25) or a low (5%) protein diet (N = 25) for 8 days. There were no significant differences in the liver GH binding capacities between the 15% and the 5% protein-fed rats, whether expressed as pmol per liver (20.6 ± 3.5 vs 14.4 ± 1.3; mean ± sem; P < 0.2; N = 5, respectively), pmol per mg DNA (1.08 ± 0.16 vs 0.84 ± 0.07; P <0.4) or fmol per mg of protein (28.98 ± 5.04 vs 30.26 ± 2.00; P > 0.5). Likewise, the affinity constants of the GH binding sites of the 15% and the 5% protein-fed rats were not significantly different (0.78 ± 0.05 vs 0.78 ± 0.07 × 109 l/mol; P > 0.5). Despite these non-significant reductions in liver GH binding sites, the IGF-I responses 24 h after sc injections of increasing doses of bovine GH were blunted in the rats fed the 5% protein diet. The maximal IGF-I response in the rats with the normal protein intake was 360 ± 30 U/I, but only 130 ± 40 U/l in the 5% protein-fed animals (P < 0.001). The blunted serum IGF-I responses to GH, together with decreased maximal stimulation in the 5% protein-fed hypophysectomized rats, support the possibility that a postreceptor defect in GH action contributes to the GH resistance in protein-calorie malnutrition.


2001 ◽  
Vol 171 (2) ◽  
pp. 299-308 ◽  
Author(s):  
S Merezak ◽  
AA Hardikar ◽  
CS Yajnik ◽  
C Remacle ◽  
B Reusens

We have demonstrated earlier that a low-protein (8% protein) diet during gestation alters fetal beta-cell development. Here, we investigated the effect of a low-protein diet as compared with a control (20% protein) diet, during gestation, on the sensitivity of fetal beta-cells against nitric oxide (NO) or interleukin-1 beta (IL-1 beta), and assessed the protective effect of taurine in vitro and in vivo. Neoformed islets from control fetuses or fetuses of dams fed a low-protein diet (LP group) were incubated with taurine, methionine or beta-alanine and then exposed to sodium nitropruside (SNP), a NO donor, or to IL-1 beta. To understand the effect of taurine in vivo, LP or control pregnant rats received 2.5% of taurine in the drinking water. Mortality and rate of apoptosis were quantified by confocal microscopy. Without treatment, rate of apoptosis was greater in LP group islets than in control islets (1.38+/-0.18% compared with 0.66+/-0.21% respectively, P<0.05). Addition of SNP 100 microM showed an augmentation in cell death, which was greater in the LP than in the control group (17.88+/-0.69% compared with 11.89+/-0.44% respectively, P<0.01). LP islets were more sensitive than control islets to IL-1 beta. Taurine was protective against SNP and IL-1 beta in both the groups, methionine provided a less protective effect than taurine, and pretreatment with beta-alanine had no protective effect. Taurine supplementation of the maternal diet reduced the rate of apoptosis induced by IL-1 beta in control islets and suppressed that induced by IL-1 beta in LP islets. Our findings indicate that a low-protein diet during gestation augments the sensitivity of fetal islet cells to NO and IL-1 beta. However, through in vitro and in vivo experiments our studies indicate that such effects can be rescued using amino acids such as taurine.


1998 ◽  
Vol 334 (1) ◽  
pp. 147-153 ◽  
Author(s):  
Céline JOUSSE ◽  
Alain BRUHAT ◽  
Marc FERRARA ◽  
Pierre FAFOURNOUX

Protein undernutrition is characterized by growth failure in young growing animals. Current evidence suggests that biosynthesis of insulin-like growth factor (IGF)-I and IGF-binding protein 1 (IGFBP-1) are key control points for nutritional regulation of growth. Here we examined the role of amino acid limitation in regulating the IGFBP-1 expression in the hepatic cell line. Our data show that leucine limitation strongly induces IGFBP-1 without affecting IGF-I and IGF-II expression in human HepG2 cells and in isolated rat hepatocytes. Depletion of arginine, cystine and all essential amino acids leads to induction of IGFBP-1 mRNA and protein expression in a dose-dependent manner. IGFBP-1 expression is significantly induced by leucine concentration in the range of that observed in the blood of rats fed a low-protein diet or in humans affected by kwashiorkor. Moreover, treatment of HepG2 cells with amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed a low-protein diet leads to a significantly higher expression of IGFBP-1. These data represent the first demonstration that an amino acid limitation, as occurs during dietary protein deficiency, induces IGFBP-1 expression in hepatic cells. Therefore, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.


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