Key result
Deletion of Dicer severely depleted white adipose tissue by inhibiting lipogenesis, but was not required for brown fat formation, revealing distinct requirements for Dicer in adipose tissues.
Dicer and microRNA biogenesis are essential for the formation of white adipose tissue but not brown adipose tissue, highlighting distinct regulatory requirements in adipogenesis.
Animal data leave open whether Dicer inhibition could selectively reduce white adipose tissue in patients; hypothesis-generating for microRNA-based metabolic therapies.
Dicer, an enzyme involved in microRNA maturation, is required for proper embryo gastrulation and tissue morphogenesis during mammalian development. Using primary cultures of fibroblasts and pre-adipocytes, we have previously shown that Dicer is essential for early stages of adipogenic cell differentiation. In this study, we have utilized Dicer-conditional mice to explore a role for Dicer and microRNA biogenesis in the terminal differentiation of adipocytes in vivo and in the formation of white and brown adipose tissue. Deletion of Dicer in differentiated adipocytes in Dicer-conditional, aP2-Cre transgenic mice reduced the level of various adipogenic-associated transcripts and inhibited lipogenesis in white adipocytes, resulting in a severe depletion of white adipose tissue in mice. In contrast, Dicer was not required in vivo for lipogenesis in brown adipose or for brown fat formation. However, Dicer deletion in brown adipose did decrease the expression of genes involved in thermoregulation. The results of our study provide genetic evidence of a role for microRNA molecules in regulating adipogenesis and reveal distinct requirements for Dicer in the formation of white and brown adipose tissue.
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Mudhasani et al. (2010) studied Adipogenesis. Deletion of Dicer vs. Wild-type/control mice (implied) was evaluated on Formation of white and brown adipose tissue and lipogenesis. Deletion of Dicer severely depleted white adipose tissue by inhibiting lipogenesis, but was not required for brown fat formation, revealing distinct requirements for Dicer in adipose tissues.
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