Location: Location not imported yet.Title: IGF-I mediated inhibition of leptin receptor expression in porcine hepatocytes) Author
Submitted to: Comparative Biochemistry and Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2008
Publication Date: 1/1/2010
Citation: Ramsay, T.G., Richards, M.P., Li, C.J., Caperna, T.J. 2010. IGF-I mediated inhibition of leptin receptor expression in porcine hepatocytes. Comparative Biochemsitry and Physiology. 155(1):43-48. Interpretive Summary: Leptin is a hormone produced by pig adipose tissue that can affect feeding behavior, animal health and reproduction. Studies in pigs have demonstrated that leptin can reduce feed intake and alter metabolism of muscle and fat. This study attempted to determine why leptin does not appear to affect liver metabolism. Incubation of swine liver cells with leptin did not alter carbohydrate or fat metabolism. As leptin must bind to a receptor to produce an effect, an examination of the expression of the liver leptin receptor was performed. Incubation of liver cells with several hormones normally present in the blood altered leptin receptor expression. As growth hormone reduced leptin receptor expression and since the liver cell does not respond to leptin, further exploration of this potential relationship was explored. Growth hormone caused the liver cells to produce the hormone insulin-like growth factor I (IGF-I). This IGF-I then acts on the liver cell to suppress leptin receptor expression in a dose responsive manner. This inhibitory effect of IGF-I resulted in altering the signaling of the leptin receptor in the liver cell to such an extent that it may block any response to leptin. Thus we conclude that the liver in swine does not respond to leptin because the liver produces IGF-I which blocks leptin signaling.
Technical Abstract: A study was conducted to elucidate hormonal control of leptin receptor gene expression in primary cultures of porcine hepatocytes. Hepatocytes were isolated from pigs (52 kg) and seeded into collagen-coated T-25 flasks. Monolayer cultures were established in medium containing fetal bovine serum for one day and switched to a serum-free medium for the remainder of the three d culture period. Previously established basal conditions were utilized that contained serum-free William’s E medium and 1 ng/ml insulin. For the final 24 hr, insulin (1 or 100 ng/ml) in combination with recombinant porcine somatotropin (pST, 100 or 500 ng/ml) or insulin-like growth factor 1 (IGF-1, 50 to 250 ng/mL) was supplemented to the medium. RNA was extracted and relative quantitative RT-PCR was performed with primers specific for the long form porcine leptin receptor. Leptin receptor expression was calculated relative to co-amplified 18S rRNA. Insulin had no effect on leptin receptor mRNA abundance (P > 0.05), while triiodothyronine increased leptin receptor mRNA abundance (P < 0.05). In contrast, pST or IGF-I treatment reduced leptin receptor mRNA abundance. Phosphorylation of ERK1/2 in response to acute leptin treatment was inhibited by a previous 24 hr exposure to IGF-I and GH. The mechanism appears to be through IGF-I as hepatocytes were demonstrated to secrete IGF-I in response to GH or insulin treatment. These data suggest that porcine hepatocytes may be insensitive to leptin stimulation due to the actions of endogenous IGF-I expression.