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Hydroxysteroid (17 ...
Hydroxysteroid (17 beta) dehydrogenase 12 is essential for metabolic homeostasis in adult mice
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Heikela, H. (author)
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Ruohonen, S. T. (author)
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Adam, M. (author)
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Viitanen, R. (author)
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Liljenback, H. (author)
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Eskola, O. (author)
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Gabriel, M. (author)
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Mairinoja, L. (author)
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Pessia, A. (author)
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Velagapudi, V. (author)
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Roivainen, A. (author)
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Zhang, F. P. (author)
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Strauss, L. (author)
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- Poutanen, Matti (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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(creator_code:org_t)
- American Physiological Society, 2020
- 2020
- English.
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 319:3
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https://journals.phy...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Hydroxysteroid 17 beta 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- dihydroceramide
- lipid
- liver
- toxicity
- weight loss
- food-intake
- hepatic steatosis
- liver-injury
- 17-beta-hydroxysteroid-dehydrogenase
- expression
- cytokine
- hsd17b12
- protein
- cells
- dihydroceramide
- Endocrinology & Metabolism
- Physiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Heikela, H.
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Ruohonen, S. T.
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Adam, M.
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Viitanen, R.
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Liljenback, H.
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Eskola, O.
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show more...
-
Gabriel, M.
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Mairinoja, L.
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Pessia, A.
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Velagapudi, V.
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Roivainen, A.
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Zhang, F. P.
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Strauss, L.
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Poutanen, Matti
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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American Journal ...
- By the university
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University of Gothenburg