A serum component mediates food restriction-induced growth attenuation.
Proper nutrition in terms of calories and essential food components is required to maximize longitudinal growth in children. Our previous study showed that prepubertal male rats subjected to 10 days of 40% food restriction (RES) exhibited a dramatic reduction in weight and epiphyseal growth plate height, as well as changes in gene expression and microRNAs (miRNAs) in the epiphyseal growth plate. These findings reversed rapidly after renewal of the regular food supply (catch-up [CU]). To further elucidate the mechanisms underlying the nutrition-growth association, serum collected from the RES and CU rats and control rats fed ad libitum (AL) was added to the culture medium of the chondrocyte cell line ATDC5 (instead of fetal calf serum). Serum from the RES group induced a reduction in cell viability (25%, P < .05) concomitant with an increase in cell differentiation compared with that for the AL group serum. The most interesting observation, in our opinion, was the significant reduction in the expression of specific miRNAs, including the chondro-specific miR-140. These effects were not observed for serum from refed (CU) rats. Serum levels of IGF-I, leptin, and fibroblast growth factor 21 were reduced by food restriction. The addition of IGF-I and leptin to the culture increased cell viability, whereas fibroblast growth factor 21 reduced it, suggesting the involvement of IGF-I, leptin, and possibly other still unidentified serum factors in chondrocyte cell growth. In conclusion, specific miRNAs respond to nutritional cues, and these effects are mediated by serum-borne factors. These results may promote the development of superior interventions for children with malnutrition and growth abnormalities.
Sackler School of Medicine (R.P., B.S., M.P., G.G.-Y.), Tel Aviv University, Tel Aviv 6997801, Israel; Felsentein Medical Research Center (B.S., M.P., G.G.-Y.), Petach Tikva 4945102, Israel; and The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes (M.P., G.G.-Y.), National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva 4920235, Israel.
Rakefet
R
Pando
Biana
B
Shtaif
Moshe
M
Phillip
Galia
G
Gat-Yablonski
D000818:Animals; D001835:Body Weight / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology; D024121:Collagen Type X / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000097:blood*; D005508:Food Deprivation; D005786:Gene Expression Regulation; D006132:Growth Plate / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D024121:Collagen Type X; D020738:Leptin; C580706:MIRN140 microRNA, rat; D035683:MicroRNAs; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I