Regulation of lipogenesis in human hepatocytes by androgens, glucocorticoids and 5α-reductase

N Nikolaou, M Nasiri, LL Gathercole, S Parajes, N Krone, G Valsamakis, G Mastorakos3, JW Tomlinson

Increased mRNA expression of FAS, ACC1 and ACC2 as well decreased CPT1 mRNA expression contribute to the increase in de novo lipogenesis that is observed
with testosterone and DHT treatment. Surprisingly, we also observed that AR overexpression alone, in the absence of ligand, also regulates hepatic lipid metabolism
by increasing both the expression of key components of the lipogenic pathway (FAS, ACC1, ACC2) and functional lipid accumulation. We have shown that
glucocorticoids decrease de novo lipogenesis in a dose-dependent manner and manipulation of 5αR2 activity can regulate lipogenesis in human hepatocytes in vitro.
These data demonstrate that androgens and glucocorticoids are able to stimulate lipid accumulation in human hepatocytes and this may be crucial in understanding
the association between PCOS and NAFLD.

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