Experimental autoimmune hearing loss

1114 The Journal of Clinical Investigation http://www.jci.org Volume 113 Number 8 April 2004 expression and restores sterol sensing (Figure 1). Upon fasting, Insig-2a levels rise, suppressing lipogenesis in a sterol-dependent fashion. Insulin cycling might be critical for the prevention of excessive lipogenesis. It creates a brief window during refeeding when Insig levels begin to decline and there is insufficient Insig-1 to suppress lipogenesis. However, with induction of Insig-1, lipogenesis is held in check. Thus, a wild-type refed animal “overshoots” its rate of lipogenesis (7). In contrast, transgenic mice overexpressing Insig-1 effectively abolish the cycling of Insig-1 expression and therefore do not overshoot lipogenesis upon refeeding (Figure 1). This leads to a dramatic 80% reduction in plasma triglycerides in the refed mice (8).