HSD17β11 regulates PLIN5-ATGL mediated lipolysis, but not hepatic lipid metabolism in mice
Hydroxysteroid 17β dehydrogenase 11 (HSD17β11) is a member of the 17β-HSD family with canonical roles in steroid metabolism. Given its predominant localization on lipid droplets, we investigated HSD17β11's role in lipid metabolism. In patients with metabolic dysfunction-associated fatty liver disease (MASLD), liver HSD17β11 levels are reduced, correlating with liver steatosis severity. HSD17β11 deletion in human cell lines increased lipid droplet size and number. This is associated with triglyceride accumulation due to impaired lipolysis and increased fatty acid uptake. Mechanistically, HSD17β11 facilitates the interaction between PLIN5 and ATGL, enabling efficient protein kinase A (PKA)-stimulated lipolysis. Surprisingly, Hsd17β11 deletion did not affect liver lipid metabolism or MASLD development in lean or obese mice. These findings demonstrate that while HSD17β11 is crucial for efficient PKA-mediated lipolysis in human cells, its deficiency appears redundant for lipid metabolism in mice.
Authors
- Geraldine Ooi (ORCID: https://orcid.org/0000-0002-4540-408X)
- Jieqiong Lou (ORCID: https://orcid.org/0000-0002-5481-198X)
- Matthew J. Watt (ORCID: https://orcid.org/0000-0003-4064-4188)
- David A. Stroud (ORCID: https://orcid.org/0000-0002-2048-3383)
- Joanna Sacharz (ORCID: https://orcid.org/0000-0002-1808-747X)
- Elizabeth Hinde (ORCID: https://orcid.org/0000-0001-8317-1152)
- Stacey N. Keenan (ORCID: https://orcid.org/0000-0001-6852-321X)
- Ayenachew Bezawork‐Geleta (ORCID: https://orcid.org/0000-0001-5404-5093)
- Ashleigh Solano (ORCID: https://orcid.org/0009-0008-0865-8874)
- Paul R. Burton (ORCID: https://orcid.org/0000-0001-7324-0695)
- Jackie Bayliss
- Natasha D Suriani
- Gio Fidellito (ORCID: https://orcid.org/0000-0001-7278-2644)
Institutions
- The University of Melbourne (AU)
- The Alfred Hospital (AU)
- Monash Alfred Psychiatry Research centre (AU)
- Victorian Clinical Genetics Services (AU)
- Murdoch Children's Research Institute (AU)
- Melbourne Health (AU)
- Monash University (AU)
- RMIT University (AU)
Publication Details
- Journal
- Journal of Lipid Research
- Published
- 2025-11-16
- DOI
- https://doi.org/10.1016/j.jlr.2025.100943
- Primary Topic
- Hormonal Regulation and Hypertension
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Diabetes Australia Research Trust
- Diabetes Australia
- Medical Research Council
- National Health and Medical Research Council