Role of FLVCR1a in gluco-lipid metabolism: exploring the interplay between liver and muscle

Feline Leukemia Virus Subgroup C receptor 1a (FLVCR1a) is a widely expressed membrane transporter. Initially identified as a heme exporter, FLVCR1a has recently been shown to import choline and ethanolamine. Previous studies have highlighted FLVCR1a's role in regulating ALAS1, the first and rate-limiting enzyme in heme biosynthesis, demonstrating its influence on ALAS1-mediated control of glucose and fatty acid oxidation, cholesterol synthesis, and the production of cytochromes, which are involved in nutrient utilization. Additionally, by importing choline and ethanolamine, FLVCR1a contributes to phospholipid homeostasis. As a result, FLVCR1a is expected to play a vital role in both cellular lipid and glucose metabolism, serving as a critical link between these two processes, whose connection remains unexplored. This positions FLVCR1a as a valuable hub, with potential implications both at the cellular level and in overall systemic gluco-lipid homeostasis. The present study leverages both liver-specific (LivKO) and skeletal muscle-specific (MusKO) Flvcr1a-null mouse models to investigate this aspect. The results obtained demonstrate that, similar to previous reports on MusKO mice muscle, LivKO mice livers show reduced glucose utilization and increased fatty acid uptake and oxidation. Furthermore, in both mouse models, the absence of FLVCR1a in liver or muscle leads to a comparable alteration of gluco-lipid metabolism in the corresponding FLVCR1a-proficient tissue. These findings underscore the importance of FLVCR1a in gluco-lipid homeostasis, possibly suggesting a role for this transporter in gluco-lipid metabolism-related diseases. Moreover, the observation of both localized tissue effects and broader systemic adaptations upon FLVCR1a depletion hints at its potential contribution to inter-organ communication.