Maternal vitamin A deficiency suppresses browning of white adipose tissue in offspring.

Beige adipocytes transiently emerge in white adipose tissue (WAT) during early postnatal development in mice (postnatal browning) independent of sympathetic innervation. However, the underlying mechanism remains unclear. Retinoic acid (RA), an active metabolite of vitamin A, has been reported to promote angiogenesis and browning. In this study, we aimed to elucidate the physiological role of vitamin A in postnatal browning. Maternal vitamin A deficiency, induced by feeding dams a vitamin A-deficient diet during pregnancy and lactation, suppressed browning in the offspring. In contrast, feeding dams a vitamin A-deficient diet only during pregnancy had no effect on the browning of the offspring. Additionally, browning was significantly suppressed by administration of a retinoic acid receptor (RAR) antagonist to pups during either the early (postnatal days 4-12) or late (postnatal days 12-20) lactation period. Maternal vitamin A deficiency and RAR inhibition during early lactation suppressed angiogenesis, which has been suggested to be required for the browning process in adults, whereas RAR inhibition during late lactation did not affect angiogenesis. These findings demonstrate that vitamin A plays a pivotal role in the induction of postnatal browning. Furthermore, we found that vitamin A affects the two-phase process of postnatal browning: promoting angiogenesis and progenitor proliferation in the early lactation period, followed by its action in the late lactation period on the differentiation of beige adipocytes, independently of angiogenesis.