Prenatal Protein Restriction Does Not Affect the Proliferation and Differentiation of Rat Preadipocytes

Aims/hypothesis Adverse events during intra-uterine life may programme organ growth and favour disease later in life. In animals, protein or energy restriction during gestation alters the development of the endocrine pancreas, even though the duration of malnutrition is different. Here, we evaluate the specific effects of both diets during different periods of gestation and the mechanisms underlying the decreased beta cell mass. Methods Pregnant Wistar rats were fed either a low-protein or a low-energy diet during the last week of gestation or throughout gestation. Fetuses and their pancreases were analysed at days 15 and 21 of gestation. Results The low-energy diet reduced the beta cell mass from 21-day-old fetuses by 33 or 56% when administered during the last week or throughout gestation, respectively. Fetal corticosterone levels were increased. At 15 days of fetal age, the number of cells producing neurogenin 3 (NEUROG3) or pancreatic and duodenal homeobox gene 1 (PDX-1) was reduced. Neither islet vascularisation nor beta cell proliferation was affected. The low-protein diet, in contrast, was more efficient in decreasing the fetal beta cell mass when given during the last week of gestation (−53%) rather than throughout gestation (−33%). Beta cell proliferation was decreased by 50% by the low-protein diet, independently of its duration, and islet vascularisation was reduced. This diet did not affect NEUROG3-or PDX-1-positive cell numbers. Conclusion/interpretation Although both diets reduced the fetal beta cell mass, the cellular mechanisms and the sensitivity windows were different. Early alteration of neogenesis due to elevated corticosterone levels is likely to be responsible for the decreased beta cell mass in low-energy fetuses, whereas impaired beta cell proliferation and islet vascularisation at later stages are implicated in low-protein fetuses. Keywords

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“…The composition and source of the diets have been described elsewhere [18]. Five groups of animals were followed.…”

Section: Methodsmentioning

confidence: 99%

Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet

et al. 2007

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“…In terms of programming effects contributing towards enhanced catch-up fat, it would be expected that in response to undernutrition in utero, adipocytes may have an enhanced ability to store fat. However, a recent study (Bieswal et al 2004) has failed to find differences in either the proliferation or lipidaccumulating properties in vitro of adipocytes isolated from growth-retarded rats compared with controls. There is some evidence that offspring of protein-restricted dams show an increased hepatic expression of lipogenic enzymes (Maloney et al 2003); however, whether permanent alterations in fuel partitioning may result following early developmental insult remains to be fully investigated.…”

Section: Low Birth Weight and Metabolic Diseasementioning

confidence: 99%

Developmental programming of energy balance and the metabolic syndrome

Cottrell

Ozanne

2007

Proc. Nutr. Soc.

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The increasing prevalence of the metabolic syndrome in numerous populations throughout the world is currently of major concern, and presents a huge global health problem. The link between low birth weight and the subsequent development of obesity, disrupted glucose homeostasis and hypertension is now well established, and there is extensive evidence supporting these associations in both epidemiological and experimental studies. Alterations in the secretion of, and responses to, the circulating hormones insulin and leptin are likely candidates in terms of disease development. The aim of current research is to define how the central and peripheral pathways in which these signals exert their effects may be disrupted following poor early growth, and how this disruption contributes to the development of metabolic disease. The present review aims to outline the existing evidence whereby alterations in early growth may programme an individual to be at increased risk of the metabolic syndrome. The development of central appetite and expenditure circuits and of peripheral metabolic tissues, are likely to play a key role in the long-term regulation of energy balance.

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“…The pregnant females were individually housed with free access to water. Dams were fed ad libitum during gestation and lactation with a control (20% w/w protein) or isocaloric low-protein (LP) diet (8% w/w protein; LP group) (Hope Farm, Woerden, the Netherlands) (18). After weaning, the progeny of both groups were fed standard chow ad libitum.…”

Section: Animals and Dietsmentioning

confidence: 99%

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

et al. 2014

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The intrauterine environment of the fetus is a preeminent actor in long-term health. Indeed, mounting evidence shows that maternal malnutrition increases the risk of type 2 diabetes (T2D) in progeny. Although the consequences of a disturbed prenatal environment on the development of the pancreas are known, the underlying mechanisms are poorly defined. In rats, restriction of protein during gestation alters the development of the endocrine pancreas and favors the occurrence of T2D later in life. Here we evaluate the potential role of perturbed microRNA (miRNA) expression in the decreased b-cell mass and insulin secretion characterizing progeny of pregnant dams fed a low-protein (LP) diet. miRNA profiling shows increased expression of several miRNAs, including miR-375, in the pancreas of fetuses of mothers fed an LP diet. The expression of miR-375 remains augmented in neoformed islets derived from fetuses and in islets from adult (3-month-old) progeny of mothers fed an LP diet. miR-375 regulates the proliferation and insulin secretion of dissociated islet cells, contributing to the reduced b-cell mass and function of progeny of mothers fed an LP diet. Remarkably, miR-375 normalization in LP-derived islet cells restores b-cell proliferation and insulin secretion. Our findings suggest the existence of a developmental memory in islets that registers intrauterine protein restriction. Hence, pancreatic failure after in utero malnutrition could result from transgenerational transmission of miRNA misexpression in b-cells.

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Prenatal Protein Restriction Does Not Affect the Proliferation and Differentiation of Rat Preadipocytes

Cited by 33 publications

References 42 publications

Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet

Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet

Developmental programming of energy balance and the metabolic syndrome

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

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