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Leptin and Cerulenin Differently Regulate Adiponectin Gene Expression in Chicken Liver and Hypothalamus

Petra Sintubin, Eddy Decuypere, Johan Buyse, Arieh Gertler, Rebekah Whitfield and Sami Dridi

Adiponectin and leptin are two adipocytokines originally found to be secreted mainly by white adipose tissue (AT) in mammals. They are involved in the control of energy homeostasis, body weight, lipid metabolism, and insulin sensitivity. The interplay between these two hormones was exclusively studied in mammals and yielded conflicting results. In birds, adiponectin and leptin are expressed not only in AT, but also in liver (for leptin) and in a wide range of tissues (for adiponectin). However, their physiological roles and relationship are still unknown. The aim of the present study was to investigate the effect of recombinant chicken leptin on adiponectin gene expression in three metabolically important tissues (liver, hypothalamus, and muscle). The effect of gender and cerulenin, the natural fatty acid synthase inhibitor which has been shown to share some molecular mediators with leptin, were also evaluated. Females exhibited significantly (P<0.05) higher levels of adiponectin mRNA in muscle and the liver, but not in the hypothalamus compared to male broiler chickens. Regardless of gender, muscle was found to contain the highest amount of adiponectin mRNA followed by the liver and hypothalamus. Continuous infusion of leptin (8 μg/ kg/h) for 6h in 3-wk-old broiler chickens significantly (P<0.05) increased plasma leptin levels, reduced food intake, and downreglated adiponectin gene expression in liver and muscle compared to the control. Cerulenin treatment (15 mg/ml) at different times significantly (P<0.05) reduced food intake. These changes were accompanied by significant (P<0.05) upregulation of hepatic adiponectin gene expression. Hypothalamic and muscle adiponectin mRNA abundance however were significantly (P<0.05) downregulated by cerulenin treatment compared to the control. Our data showed that adiponectin gene expression is regulated by gender, leptin, and cerulenin in a tissue-specific manner. It also suggests that cerulenin does not mimic leptin by downregulating hepatic adiponectin, however it does mimic it by reducing food intake.