High-calorie total parenteral nutrition reduces hepatic insulin-like growth factor-I mRNA and alters serum levels of insulin-like growth factor-binding protein-1, -3, -5, and -6 in the rat.
High-calorie total parenteral nutrition (TPN) is associated with hepatic dysfunction and steatosis. Because TPN-induced steatosis might compromise hepatic expression of insulin-like growth factor-I (IGF-I) and thereby limit its potential nutritional benefit, we examined hormonal and IGF-I responses in male Sprague-Dawley rats (270 to 300 g) fed by continuous intravenous infusion with high-calorie, high-dextrose (350 kcal/kg) TPN solutions for O (control), 2, 4, and 8 days. Since IGF-binding proteins (IGFBPs) are thought to modulate the biological effects of IGFs in target tissues, we also determined serum levels of IGFBPs. Animals developed hepatic steatosis after 2 to 8 days of TPN, as reflected by a sevenfold to 15-fold increase in hepatic triacylglycerol content (P < .001 v control on each day). Serum corticosterone and insulin levels were significantly higher after 2 and 4 days of TPN, whereas serum growth hormone levels were reduced after 4 and 8 days. Serum IGF-I levels were not significantly different during TPN. However, there was a coordinate reduction in the three major hepatic IGF-I transcripts (7.0, 1.9, and 1.0 kb) after 2, 4, or 8 days of TPN, and IGF-I transcripts corresponding to multiple initiation sites within exons 1 and 2 were coordinately downregulated with TPN. Western ligand blotting indicated that serum levels of 38K to 43K, 30K to 34K, and 24K IGFBPs were increased approximately twofold after 4 and 8 days of TPN as compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)
Ney
D M
DM
Department of Nutritional Sciences, University of Wisconsin-Madison 53706.
Yang
H
H
Smith
S M
SM
Unterman
T G
TG
D000818:Animals; D002352:Carrier Proteins / Q000097:blood*; D003345:Corticosterone / Q000097:blood; D015536:Down-Regulation; D002149:Energy Intake; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000032:analysis
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D003345:Corticosterone