Consequences of dietary protein deficiency on IGF-IGFBP system in foetal rat liver
(2004)
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- Abstract
- Fetal growth retardation still represents a high risk of early mortality and morbidity. It is associated with the appearance of a cluster of metabolic disorders commonly named "the metabolic syndrome" at adult age including type 2 diabetes. Understanding the mechanisms of fetal growth retardation could have its importance in prevention of persons with metabolic syndrome and related diseases namely type 2 diabetes and cardiovascular disease. Regulation of fetal growth is complex and multifactorial. Diverse factors, including environmental factors lead to abnormal intrauterine growth. Maternal protein deficiency is one of these influences that result to low birth weight as well as to altered organs such as liver, pancreas and adipose tissue in the offspring. There is evidence that Insulin like growth factors and Insulin like growth factors Binding Proteins regulate tissue as well as overall fetal growth. In several animal models of intrauterine growth retardation due to maternal undernutrition (calorie and/or protein), decreased IGF-I and/or elevated IGFBPs are observed in late fetal gestation. However, in these studies a general food deprivation or a severe hypocaloric protein restriction was applied. In the present work we examined the influence of a moderate and specific isocaloric protein deficiency (8% vs 20%) on the fetal IGF system. In our Low Protein (LP) growth retarded fetuses, we found in vivo that IGF-I level was lower whereas the main binding proteins (IGFBP-1 & IGFBP-2) in the fetus that modulate IGFs by preventing their action are elevated. This suggested that altered IGF-I and IGFBPs could lead to decreased fetal growth in our LP model. Despite this important finding, the mechanisms by which maternal undernutrition and protein deficiency, in particular, result in the altered fetal IGF system are not well understood. For this purpose and because the liver is the main organ in the production of IGFs and IGFBPs, we set up a validated culture system of "highly purified" fetal hepatocytes to study the regulation of fetal IGFs and IGFBPs. Among factors studied, hormones (insulin, glucocorticoids, prolactin) as well as some specific amino acids (branched chain amino acids, leucine and taurine) that appear to be affected by maternal undernutrition were examined. Overall, we found that insulin, glucocorticoids as well as prolactin modulate IGFs as well as IGFBPs in vitro and could therefore contribute to the abnormal profile of fetal IGF system seen in vivo in LP fetuses. A similar proposal could be attributed to branched chain amino acids, leucine and taurine with some caution since the most marked effects were observed within elevated range of these amino acids. Furthermore, the low protein diet appeared to affect profoundly the fetal IGF system as well as its regulation. When LP cultured hepatocytes were kept under similar culture conditions as control cells during the whole duration of culture, the altered production of IGF-I and IGFBPs (-1 & -2) was maintained, stressing some programming as occurred in utero. Also, a resistance of IGFBPs to the action of prolactin has been observed in cultured LP hepatocytes since they did not respond to the action of hormone as they did in control cultures. This may indicate that maternal protein deficiency could alter the hormonal sensitivity which may be characteristic of intrauterine growth retardation.
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El Khattabi, I. (2004). Consequences of dietary protein deficiency on IGF-IGFBP system in foetal rat liver. https://hdl.handle.net/2078.5/97521