Abstract
Carotenoids, essential nutrients for eye health, are absorbed in the intestine to support vitamin A homeostasis and provide cellular protection. This process involves the lipid transporters scavenger receptor class B type 1 (SR-B1, encoded by Scarb1 gene) and Niemann-Pick C1-Like 1 (NPC1L1), which load these dietary lipids into the plasma membrane of intestinal enterocytes. However, the precise contribution of these transporters to carotenoid absorption, the putative involvement of Aster proteins in their downstream movement, and the interactions with their metabolizing enzymes, β-carotene oxygenase 1 (BCO1) and β-carotene oxygenase 2 (BCO2), remain incompletely understood. Here, we investigated carotenoid metabolism in the mouse intestine using pharmacological and genetic approaches. We observed that ezetimibe, an NPC1L1 inhibitor, reduced zeaxanthin but did not affect β-carotene absorption. Aster-C, highly expressed in enterocytes, bound zeaxanthin in biochemical assays. In mice, Aster-C deficiency led to upregulation of Gramd1b (Aster-B) expression and increased zeaxanthin bioavailability. We further showed that BCO1 directly interacted with membranes to extract β-carotene for retinoid production, indicating that vitamin A production is Aster protein-independent. This observation is consistent with the finding that the intestine-specific transcription factor ISX, the master regulator of vitamin A production, controlled Scarb1 and Bco1 expression but had no effect on Gramd1a, b, or c, encoding Aster proteins in intestinal enterocytes. Together, our study revealed distinct pathways for β-carotene and zeaxanthin absorption and metabolism, offering new insights into carotenoid bioavailability and potential strategies to optimize dietary carotenoid intake for improved eye health.