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

Khattabi, Ilham El; Gregoire, Francine M.; Remacle, Claude; Reusens, Brigitte

doi:10.1152/ajpendo.00037.2003

Cited by 59 publications

(64 citation statements)

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“…Expansion of b cell mass in late gestation is dependent on tropic growth factors such as insulin-like growth factor (IGF)-II, which is reduced following LP diet (Petrik et al 1999). This is not specific to pancreas, since hepatocytes from offspring of LP-fed animals showed a reduced rate of proliferation, a lower expression of IGF-I, and an increased synthesis of IGF-binding proteins (El-Kattabi et al 2003). The relevance of impaired growth factor presence or action to the reduction in islet mass has been demonstrated by its reversal following the administration of the glucagonlike polypeptide-1 analog, exendin 4, to growth retarded, neonatal offspring from mothers subjected to uterine vessel occlusion (Stoffers et al 2003).…”

Section: Discussionmentioning

confidence: 96%

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

Chamson-Reig¹,

Thyssen²,

Arany³

et al. 2006

Journal of Endocrinology

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Restriction of dietary protein during gestation and lactation in the rat results in a reduction in b cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1-2)), the second week only (LP (2)), or the third week (LP (3)). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 mm 2 ) and medium (between 5000 and 10 000 mm 2 ) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of b cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in midgestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both b cell development and insulin gene transcription, was decreased in female offspring following LP (1-2) and LP (3), but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of b cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of b cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.

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Section: Discussionmentioning

confidence: 96%

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

Chamson-Reig¹,

Thyssen²,

Arany³

et al. 2006

Journal of Endocrinology

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“…IGFs are mitogenic for beta cell and act as cell survival factors by inhibiting apoptosis [38]. IGFs are perturbed in plasma and hepatocytes of fetus from LP-fed mothers [39]. The pancreatic expression of Igf2 mRNA and protein was lower in LP fetus and neonates [13].…”

Section: Discussionmentioning

confidence: 99%

The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation

et al. 2008

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Aims/hypothesis Events during fetal life may in critical time windows programme tissue development leading to organ dysfunction with potentially harmful consequences in adulthood such as diabetes. In rats, the beta cell mass of progeny from dams fed with a low-protein (LP) diet during gestation is decreased at birth and metabolic perturbation lasts through adulthood even though a normal diet is given after birth or after weaning. Maternal and fetal plasma taurine levels are suboptimal. Maternal taurine supplementation prevents these induced abnormalities. In this study, we aimed to reveal changes in gene expression in fetal islets affected by the LP diet and how taurine may prevent these changes. Methods Pregnant Wistar rats were fed an LP diet (8% [wt/wt] protein) supplemented or not with taurine in the drinking water or a control diet (20% [wt/wt] protein). At 21.5 days of gestation, fetal pancreases were removed, digested and cultured for 7 days. Neoformed islets were collected and transcriptome analysis was performed. Results Maternal LP diet significantly changed the expression of more than 10% of the genes. Tricarboxylic acid cycle and ATP production were highly targeted, but so too were cell proliferation and defence. Maternal taurine supplementation normalised the expression of all altered genes. Conclusions/interpretation Development of the beta cells and particularly their respiration is modulated by the intrauterine environment, which may epigenetically modify expression of the genome and programme the beta cell towards a pre-diabetic phenotype. This mis-programming by maternal LP diet was prevented by early taurine intervention.Keywords Diabetes . Early programming . Fetal islets . Maternal low-protein diet . Rats . Taurine . Transcriptome Abbreviations EST expressed sequence tag LP low protein LPT low-protein diet supplemented with taurine SAM significance analysis of microarrays TCA tricarboxylic acid Diabetologia (2008) 51:836-845

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“…Calorie restriction has been found to either decrease or not IGF levels at birth and to increase or not IGF binding proteins (IGFBPs). 55,56 Protein restriction decreased plasma IGF-1 levels in the progeny at birth, 57,58 as well as augmented the abundance of IGFBP-1 and -2, the liver production of which being regulated in part by insulin and glucocorticoids. 58 A third pathway of generating obesity in children and adult is a modification in the population of fat cell precursors.…”

Section: Animal Models For Programming Of Obesitymentioning

confidence: 98%

“…55,56 Protein restriction decreased plasma IGF-1 levels in the progeny at birth, 57,58 as well as augmented the abundance of IGFBP-1 and -2, the liver production of which being regulated in part by insulin and glucocorticoids. 58 A third pathway of generating obesity in children and adult is a modification in the population of fat cell precursors. If an enlargement of the adipose cell due to fat accumulation may contribute to obesity, the multiplication and differentiation of precursor cells has a much greater influence.…”

Section: Animal Models For Programming Of Obesitymentioning

confidence: 98%

Programming of obesity and cardiovascular disease

2004

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BACKGROUND: There is evidence that malnutrition in early life induces a growth retardation leading, in adult life, to manifest components of the metabolic syndrome. However, the impact on obesity seems less clearly established. OBJECTIVE: To review the effects of foetal and postnatal malnutrition on the programming of obesity in the context of the metabolic syndrome, as well as the link between central obesity and cardiovascular diseases. METHODS: Included in the review were recent papers exploring the mechanisms linking maternal nutrition with impaired foetal growth and later obesity, cardiovascular disease, hypertension and diabetes in humans and animals. RESULTS: The programming of obesity during foetal and early postnatal life depends of the timing of maternal malnutrition as well as the postnatal environment. Obesity arises principally in offspring submitted to malnutrition during early stages of gestation and which presented early catch-up growth. The programming may involve the dysregulation of appetite control or the hormonal environment leading to a context favourable to obesity development (hypersecretion of corticosteroids, hyperinsulinaemia and hyperleptinaemia and anomalies in the IGF axis). Adipose tissue secretes actively several factors implicated in inflammation, blood pressure, coagulation and fibrinolysis. The programmed development of intra-abdominal obesity after early growth restriction may thus favour higher prevalence of hypertension and cardiovascular diseases. CONCLUSIONS: Abdominal obesity appears in malnourished offspring and is aggravated by early catch-up growth. Higher rates of intra-abdominal obesity observed after growth restriction may participate to hypertension and create atherothrombotic conditions leading to the development of cardiovascular diseases.

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

Cited by 59 publications

References 64 publications

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation

Programming of obesity and cardiovascular disease

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