Barrier perturbation stimulates epidermal cholesterol synthesis, which plays an important role in restoring barrier function. In the present study, we examined whether changes in serum cholesterol levels or nutrition regulate epidermal cholesterol synthesis in hairless mice. Serum cholesterol levels were lowered by 50% after injection with 4-aminopyrazolo (3,4-d) pyrimidine and were increased by 51% by feeding an atherogenic diet. In contrast to most other tissues, cholesterol synthesis in the epidermis and dermis was not inhibited by elevations or stimulated by decreases in serum cholesterol levels. Additionally, feeding a high-cholesterol diet did not decrease epidermal or dermal cholesterol synthesis. However, fasting significantly decreased both epidermal (38%) and dermal (34%) cholesterologenesis. Furthermore, barrier recovery after acetone disruption of the barrier was impaired in fasted animals. However, treatment with topical lipids did not restore barrier repair rate to normal, indicating that factors in addition to lipids are necessary to overcome the effects of fasting. These results demonstrate that cholesterol synthesis in the epidermis and dermis is regulated independently of changes in serum cholesterol levels.
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