4.7 Article

Deciphering influences of testosterone and dihydrotestosterone on lipid metabolism genes using brown trout primary hepatocytes

Journal

AQUATIC TOXICOLOGY
Volume 235, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.aquatox.2021.105819

Keywords

Androgens; Fatty acids; Liver; Fish; Sex-steroids

Funding

  1. FCT [UIDB/04423/2020, UIDP/04423/2020]
  2. ERDF
  3. Doctoral Programme in Pathology and Molecular Genetics, of the ICBAS - University of Porto

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The study reveals that androgens may impact gene expression related to lipid metabolism in fish liver, including fatty acid activation, lipid synthesis, lipid transport, and fatty acid oxidation.
Despite of physiological and toxicological relevance, the potential of androgens to influence fish lipid metabolism remains poorly explored. Here, brown trout primary hepatocytes were exposed to six concentrations (1 nM to 100 mu M) of dihydrotestosterone (DHT) and testosterone (T), to assess changes in the mRNA levels of genes covering diverse lipid metabolic pathways. Acsl1, essential for fatty acid activation, was up-regulated by T and DHT, whereas the lipogenic enzymes FAS and ACC were up-regulated by the highest (100 mu M) concentration of T and DHT, respectively. ApoA1, the major component of high-density lipoprotein (HDL), was down-regulated by both androgens. PPAR gamma, linked to adipogenesis and peroxisomal beta-oxidation, was down-regulated by T and DHT, while Acox1-3I, rate-limiting in peroxisomal beta-oxidation, was down-regulated by T. Fabp1, StAR and LPL were not altered. Our findings suggest that androgens may impact on lipid transport, adipogenesis and fatty acid beta-oxidation and promote lipogenesis in fish liver.

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