A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Hydroxysteroid (17β) dehydrogenase 12 is essential for metabolic homeostasis in adult mice
Tekijät: Heikelä Hanna, Ruohonen Suvi T, Adam Marion, Viitanen Riikka, Liljenbäck Heidi, Eskola Olli, Gabriel Michael, Mairinoja Laura, Pessia Alberto, Velagapudi Vidya, Roivainen Anne, Zhang Fu-Ping, Strauss Leena, Poutanen Matti
Julkaisuvuosi: 2020
Journal: American Journal of Physiology : Endocrinology and Metabolism
Tietokannassa oleva lehden nimi: American journal of physiology. Endocrinology and metabolism
Lehden akronyymi: Am J Physiol Endocrinol Metab
Vuosikerta: 319
Numero: 3
Aloitussivu: E494
Lopetussivu: E508
Sivujen määrä: 15
ISSN: 0193-1849
eISSN: 1522-1555
DOI: https://doi.org/10.1152/ajpendo.00042.2020
Verkko-osoite: https://doi.org/10.1152/ajpendo.00042.2020
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/48966942
Hydroxysteroid 17β dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously, we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within 6 days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males, 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity, specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Proinflammatory cytokines, such as interleukin-6 (IL-6), IL-17, and granulocyte colony-stimulating factor, were increased in the HSD17B12cKO mice indicating an inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides, and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
