Dietary regulation of stearoyl-CoA desaturase 1 gene expression in mouse liver.

Abstract

Expression of the murine liver stearoyl-CoA desaturase gene (SCD1) is induced upon feeding fasted mice a fat-free, high carbohydrate diet (Ntambi, J. M., Buhrow, S. A., Kaestner, K. H., Christy, R. J., Sibley, E., Kelly, T. J., and Lane, M.D. (1988) J. Biol. Chem. 263, 17291-17300). In the present study, SCD1-specific RNA riboprobes and cDNA probes were used to study the mechanism for the induction of SCD1 mRNA. Based on the time course of induction, the SCD1 mRNA increased from 2-fold within 6 h to 45-fold within 36 h. Nuclear run-on transcription studies showed that the accumulation of SCD1 mRNA after refeeding starved mice a fat-free, high carbohydrate diet was a consequence of the transcriptional activation of the SCD1 gene. The SCD1 mRNA level decreased rapidly (t1/2 = approximately 4 h) within 24 h when mice fed the fat-free, high carbohydrate diet were switched to a regular chow diet. Furthermore, when the fat-free diet was supplemented with triacylglycerides containing polyunsaturated fatty acids, the transcription of the SCD1 gene and the induction of the SCD1 mRNA were significantly blunted. Triacylglycerides containing saturated and monounsaturated fatty acids were without dramatic effects. In contrast, synthesis of liver albumin mRNA was little affected by any of these dietary variations, indicating that the observed changes in the transcription of the SCD1 gene and mRNA levels were specific. These data demonstrate that both dietary carbohydrates and polyunsaturated fatty acids or their metabolites directly or indirectly regulate the expression of the SCD1 gene in mouse liver.