Regulation of Retinoid Homeostasis

atRA regulates retinoid homeostasis. It induces LRAT transcription ~ 100-fold and induces CRBP(I) transcription. These may be housekeeping functions that maintain retinol esterification and handling during vitamin A sufficiency. On the other hand, induction of CYP26A1 by atRA can be viewed both as a general mechanism of clearance and as a site-specific mechanism to maintain an environment during specific stages of development.

Several xenobiotics, including ethanol and poly-chlorinated biphenyls, reduce RE stores, possibly through enhancing atRA catabolism by inducing CYP. In addition, clofibrate, a ligand of PPARa (peroxisome proliferator activated receptor), causes a remarkably rapid depletion of liver retinoids and decreases TTR mRNA fourfold. In contrast, PPAR7, expressed in liver stellate cells among others, induces transcription of carotene 15,15'-monooxygenase. PPAR7 also induces expression of CRBP(I), CRBP(II), LRAT, and RARft. These actions of PPARa and -7 with retinoids reflect their effects on lipid metabolism: PPARa enhances fatty acid cata-bolism, whereas PPAR7 enhances adipogenesis and fatty acid storage.

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