Abstract
Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-β superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1α was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells. Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism.
Highlights
Obesity has reached epidemic proportions world-wide, with more than a billion adults being overweight, and over 300 million adults classified as obese (BMI >30 kg/m2) [1]
Journal of Lipid Research Volume 55, 2014 375 different developmental origins. These are classical brown adipocytes, which are found in the interscapular regions, and pockets of uncoupling protein 1 (UCP1)-positive adipocytes that are found within white adipose tissue (WAT) depots [12,13,14,15,16,17]
We investigated whether Fst expression is regulated during brown adipocyte differentiation
Summary
Obesity has reached epidemic proportions world-wide, with more than a billion adults being overweight (defined as a BMI greater than 25 kg/m2), and over 300 million adults classified as obese (BMI >30 kg/m2) [1]. Journal of Lipid Research Volume 55, 2014 375 different developmental origins These are classical brown adipocytes, which are found in the interscapular regions, and pockets of UCP1-positive adipocytes that are found within white adipose tissue (WAT) depots [12,13,14,15,16,17]. These inducible brown-like adipocytes known as “brite” (brown-within-white) or “beige” adipocytes possess many of the biological and morphological characteristics of classical brown adipocytes. Some factors that promote the “browning” of WAT have been identified, including PPAR␥ agonists, SirT1-dependent deacetylation of PPAR␥, activation of the hypothalamic-adipocyte axis, and loss of myostatin (Mst) and neuronatin [13,14,15,16,17]
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