ENERGY-BALANCE AND LIPID-METABOLISM IN TRANSGENIC MICE BEARING AN ANTISENSE GCR GENE CONSTRUCT

Energy balance and lipid metabolism were investigated in transgenic mi ce bearing an antisense glucocorticoid receptor (GCR) gene construct t hat impairs the normal expression of the GCR gene. Food intake was rec orded during the 15 days preceding decapitation of adult normal and tr ansgenic mice, and feces were collected to derive the digestible energ y intake. Body composition measurements consisted of the determination of energy, protein, and fat content of the carcass. Carcass energy wa s determined by bomb calorimetry, whereas carcass protein was measured by the Kjeldahl procedure. Energy expenditure was estimated from the continuous oxygen consumption (VO2) monitoring over a 24-h period. Lip oprotein lipase (LPL) activity was quantified in epididymal white adip ose tissue (WAT), heart, and vastus lateralis muscle (VLM) by measurin g the in vitro hydrolysis of labeled triolein in the presence of tissu e homogenates. Norepinephrine (NE) content of both interscapular brown adipose tissue (BAT) and heart were determined by high-performance li quid chromatography (HPLC). Energy intake and expenditure were signifi cantly lower in transgenic mice than in controls. Concurrently, both f at content and total energy of the carcasses were significantly higher in the transgenic animals. In comparison with normal mice, heart and VLM LPL activity was significantly reduced in transgenic mutants. Ther e was no difference between groups in LPL activity in WAT. Finally, he art and BAT NE contents were lower in transgenic animals than in contr ol mice. These results suggest that a defective GCR system may affect energy balance through increasing energetic efficiency, and they empha size the modulatory effects of hypothalamic-pituitary-adrenal axis cha nges on muscle LPL activity.