title: Nutritional catch-up growth.
abstract: Malnutrition, marked by variant nutrient deficiencies, is considered a leading cause of stunted growth worldwide. In developing countries, malnutrition is caused mainly by food shortage and infectious diseases. Malnutrition may also be found in the developed world, where it is due mostly to prematurity, chronic diseases, and anorexia nervosa. In most cases, when food consumption is corrected, spontaneous catch-up (CU) growth occurs. However, CU growth is not always complete, leading to growth deficits. Therefore, it is important to understand the mechanisms that govern this process. Using a rat model of food restriction followed by refeeding, we established a nutrition-induced CU growth model. Levels of leptin and insulin-like growth factor-1 were found to significantly decrease when food was restricted and to increase already 1 day after refeeding. Gene expression analysis of the growth plate revealed that food restriction specifically affects transcription factors such as the hypoxia inducible factor-1 and its downstream targets on the one hand, and global gene expression, indicating epigenetic regulation, on the other. Food restriction also reduced the level of several microRNAs, including the chondrocyte-specific miR-140, which led to an increase in its target, SIRT1, a class III histone deacetylase. These findings may explain the global changes in gene expression observed under nutritional manipulation. We suggest that multiple levels of regulation, including transcription factors, epigenetic mechanisms, and microRNAs respond to nutritional cues and offer a possible explanation for some of the effects of food restriction on epiphyseal growth plate growth. The means whereby these components sense changes in nutritional status are still unknown. Deciphering the role of epigenetic regulation in growth may pave the way for the development of new treatments for children with growth disorders.
authors: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Children's Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel. galiagy@post.tau.ac.il
authors: Galia
authors: G
authors: Gat-Yablonski
authors: Rakefet
authors: R
authors: Pando
authors: Moshe
authors: M
authors: Phillip
mesh_terms: D000818:Animals; D019049:Developed Countries; D003906:Developing Countries; D044127:Epigenesis, Genetic; D006132:Growth Plate / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D044342:Malnutrition / Q000503:physiopathology* / Q000517:prevention & control; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D018977:Micronutrients / Q000008:administration & dosage / Q000172:deficiency; D009752:Nutritional Status; D051381:Rats; D020123:Sirolimus / Q000378:metabolism
chemical_list: D020738:Leptin; D035683:MicroRNAs; D018977:Micronutrients; D007334:Insulin-Like Growth Factor I; D020123:Sirolimus