Spot 14 gene deletion increases hepatic de novo lipogenesis

Previous studies have investigated the relationship between the Spot 14 gen e and hepatic lipogenesis. Those studies found that the Spot 14 protein was induced when lipogenesis was induced and suggested that induction of the S pot 14 protein was required for induction of hepatic lipogenesis by thyroid hormone and dietary carbohydrate. Analysis of those findings led us to hyp othesize that the Spot 14 gene is required for induced hepatic de novo lipo genesis in vivo. To test this hypothesis, we created an in vivo deletion of the Spot 14 gene in mice using gene-targeting technology. Southern blot an alysis showed that the Spot 14 gene was disrupted. Northern blot analysis s howed that this disruption ablated expression of intact hepatic Spot 14 mRN A. In contrast to our hypothesis, acute thyroid hormone administration led to comparable induction of hepatic lipogenic enzyme mRNAs between the wildt ype and knockout mice. Furthermore, long-term treatment with both thyroid h ormone and a diet promoting lipogenesis led to enhanced lipogenic enzyme ac tivity and a greater rate of hepatic de novo lipogenesis in the knockout, c ompared with the wild-type, mice. Although these data indicate that the Spo t 14 protein is not required for induced hepatic de novo lipogenesis, they also suggest that Spot 14 plays some role in this process. It is possible t hat alternative pathways that complement the loss of the Spot 14 protein ar e present, and in the absence of Spot 14, these alternative pathways overco mpensate to produce an enhanced rate of induced lipogenesis.