Submitted on April 23, 2007
Revised on September 25, 2007
Accepted on October 1, 2007
Methionine restriction effects on 11
-HSD1 activity and lipogenic/lipolytic balance in F344 rat adipose tissue
Carmen E. Perrone, Dwight A. L. Mattocks, George Hristopoulos, Jason D. Plummer, Rozlyn A. Krajcik, and Norman Orentreich
Cellular Biology, Orentreich Foundation, Cold Spring-on-Hudson, NY 10516
Corresponding Author: perrone{at}orentreich.org
Methionine restriction (MR) limits age-related adiposity in Fischer344 (F344) rats. To assess the mechanism of adiposity resistance, the effect of MR on adipose tissue (AT) 11ß-hydroxysteroid dehydrogenase-1 (11ß-HSD1) was examined. MR induced 11ß-HSD1 activity in all ATs correlating with increased tissue corticosterone. However, an inverse relationship between 11ß-HSD1 activity and adipocyte size was observed. Because dietary restriction controls lipogenic and lipolytic rates, MR’s effects on lipogenic and lipolytic enzymes were evaluated. MR increased adipose triglyceride lipase (ATGL) and acetyl-CoA carboxylase (ACC) protein levels, but induced ACC phosphorylation at serine residues that render the enzyme inactive, suggesting alterations of basal lipolysis and lipogenesis. In contrast, no changes in basal or phosphorylated hormone-sensitive lipase (HSL) levels were observed. ACC phosphorylated sites were specific for AMP-activated protein kinase (AMPK); therefore, AMPK activation was evaluated. Significant differences in AMPKa protein, phosphorylation and activity levels were observed only in retroperitoneal fat from MR rats. No differences in protein kinase A (PKA) phosphorylation and intracellular cAMP levels were detected. In vitro studies revealed increased lipid degradation and a trend toward increased lipid synthesis, suggesting the presence of a futile cycle. In conclusion, MR disrupts the lipogenic/lipolytic balance, contributing importantly to adiposity resistance in F344 rats.
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