Postnatal catch-up growth induced by growth hormone and insulin-like growth factor-I in rats with intrauterine growth retardation caused by maternal protein malnutrition

In this study, we examined the effects of exogenous IGF-I and GH on postnatal growth of rat pups with intrauterine growth retardation due to gestational protein restriction. From birth until weaning (d 23), pups born from dams fed ad libitum a low (5% casein; P5 pups) or a normal protein diet (20% casein; P20 controls) were cross-fostered to well nourished lactating dams. On d 2, the litters (n = 6/dietary group) were reduced in size to 6 pups, and littermates received, through postnatal d 23, two daily s.c. injections of bovine GH (2.5 microg/g of body weight (BW)/day), human IGF-I (1.8 microg/g of BW/day), or saline. At birth, BW and tail length (TL) of P5 pups were markedly decreased (to 72 and 70% of controls, respectively; p < 0.001). Despite food rehabilitation, stunting of body growth was still apparent on d 23 in the saline-injected P5 rats (BW and TL: 76 and 83% of age-matched saline-injected controls; p < 0.01). Serum IGF-I (-51%; p < 0.001) and weight of liver, heart, kidney, brain, and thymus (-13 to -35%; p < 0.01) were also reduced. Administration of GH in P5 rats raised their serum IGF-I (1-fold) to levels observed in saline-injected controls, and restored normal BW and TL (94 and 98% of controls, respectively), and organ weight (91-107% of those of controls). Injections of IGF-I in P5 rats increased after 1 h their serum IGF-I to levels 3 times greater than in saline-injected controls, and resulted in normalization of BW and TL (94 and 96% of controls), and organ weight (92-111% of controls). In P20 controls, 3-wk GH and IGF-I injections significantly increased serum IGF-I (0.6- and 2-fold increases, respectively), BW (14 and 11%), TL (12 and 11%), and organ weight (+10 to 30%) compared with saline-injected rats (p < 0.01). We conclude that under conditions of adequate nutrition, both GH and IGF-I may equally promote postnatal catch-up growth in rats with intrauterine growth retardation caused by gestational protein malnutrition

Long-term effects of gestational protein malnutrition on postnatal growth, insulin-like growth factor (IGF)-I, and IGF-binding proteins in rat progeny.

We examined the long-term effects of dietary protein restriction during rat pregnancy on serum IGF-I, serum IGF binding proteins, and liver IGF-I gene expression during postnatal development. Pregnant Wistar rats were fed ad libitum throughout gestation a normal (20% casein diet; P20 controls) or a low (5% casein; P5) protein diet. At birth, the pups from both P20 and P5 dams were cross-fostered to well nourished lactating dams, and litters (n = 5/dietary group) were reduced in size to 6 pups. After weaning (d 22), the pups were fed the control diet ad libitum. The pups were killed at 8, 22, and 63 d of age. Gestational protein restriction caused significant growth retardation and mortality in newborn pups. Despite food rehabilitation during the suckling period (d 0-22), body weight, tail length, and the weight of liver, heart, kidney, and brain in the P5 pups remained significantly reduced at 8 and 22 d (-17 to -35%) compared with control pups. At the same time, serum and liver IGF-I concentrations in the P5 pups (on d 8: 100 +/- 9 ng/mL and 11 +/- 1 ng/g, respectively; on d 22: 340 +/- 20 ng/mL and 42 +/- 3 ng/g) were lower than in age-matched controls (on d 8: 170 +/- 12 ng/mL and 26 +/- 2 ng/g; on d 22: 470 +/- 30 ng/mL and 73 +/- 5 ng/g), although liver IGF-I mRNA abundance was not affected. After long-term food rehabilitation (d 63), tail length and organ weight recovered, and serum and liver IGF-I concentrations were normalized. However, although the P5 rats had resumed a normal growth rate, their body weight remained lower than in the controls. There were no differences in serum IGF binding proteins 1-4, insulin, and GH concentrations between the groups at any age studied. These results suggest that reduction in serum IGF-I may contribute to the reduced somatic and organ growth observed in rats after gestational protein malnutrition, and further support a role for IGF-I in the control of catch-up growth

Early environmental factors and rheumatoid arthritis

The precise cause of autoimmune diseases such as rheumatoid arthritis (RA) remains uncertain. In recent years there has been extensive investment in pursuing genes important in RA. However, estimates suggest that the risk of developing RA is at most 50% determined by genes. There has been limited success defining the environmental factors important in developing RA. We hypothesize that this lack of success may be due to a concentration on the time around disease onset. There is evidence of production of the autoantibodies rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) and increased levels of C-reactive protein (CRP) years before RA becomes clinically apparent. In addition, early life events including intrauterine growth retardation (IUGR) may have long lasting effects on immune function. We review the evidence that the early environment through effects on growth and infectious exposure may influence the likelihood of developing autoimmune diseases such as R

Programming of obesity and cardiovascular disease.

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