Normal Fur Development and Sebum Production Depends on Fatty Acid 2-Hydroxylase Expression in Sebaceous Glands
Open accessAbstract
2-Hydroxylated fatty acid (HFA)-containing sphingolipids are abundant in mammalian skin and are believed to play a role in the formation of the epidermal barrier. Fatty acid 2-hydroxylase (FA2H), required for the synthesis of 2-hydroxylated sphingolipids in various organs, is highly expressed in skin, and previous in vitro studies demonstrated its role in the synthesis of HFA sphingolipids in human keratinocytes. Unexpectedly, however, mice deficient in FA2H did not show significant changes in their epidermal HFA sphingolipids. Expression of FA2H in murine skin was restricted to the sebaceous glands, where it was required for synthesis of 2-hydroxylated glucosylceramide and a fraction of type II wax diesters. Absence of FA2H resulted in hyperproliferation of sebocytes and enlarged sebaceous glands during hair follicle morphogenesis and anagen (active growth phase) in adult mice. This was accompanied by a significant up-regulation of the epidermal growth factor receptor ligand epigen in sebocytes. Loss of FA2H significantly altered the composition and physicochemical properties of sebum, which often blocked the hair canal, apparently causing a delay in the hair fiber exit. Furthermore, mice lacking FA2H displayed a cycling alopecia with hair loss in telogen. These results underline the importance of the sebaceous glands and suggest a role of specific sebaceous gland or sebum lipids, synthesized by FA2H, in the hair follicle homeostasis.
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In Fa2h KO mice, neither the skin phenotype nor reduced AS levels in skin were observed.
“In Fa2h KO mice, neither the skin phenotype nor reduced AS levels in skin were observed (53).”
From Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS (2020) · cites this paper as [53]
In “Delayed Fur Emergence and Cyclic Alopecia in FA2H-deficient Mice” (page unavailable), the paper reports delayed fur development and repeated hair loss in Fa2h knockout mice—a skin phenotype, contrary to the claim. Its lipid analysis also reports reduced hydroxylated glucosylceramides in total skin, although hydroxylated ceramides showed no obvious change. The copy does not identify these measurements as “AS levels.” (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn that report, it is likely that BS, but not AS, was measured, because AS levels were determined by TLC or MS analysis without LC separation.
“In that report, however, it is likely that BS, but not AS, was measured, because AS levels were determined by TLC or MS analysis without LC separation (53).”
From Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS (2020) · cites this paper as [53]
The Experimental Procedures (page not available) describe TLC analysis and direct injection into the mass spectrometer, supporting the claim that no LC separation preceded MS. The paper groups shorter-chain hydroxylated sphingolipids as α-hydroxy based on chain length, but does not establish that the measured material was likely BS rather than AS. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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- Authors
- Maier, H., Meixner, M., Hartmann, D., Sandhoff, R., Wang-Eckhardt, L., Zöller, I., Gieselmann, V., & Eckhardt, M.
- Affiliations
- University of Bonn (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Eckhardt, Matthias
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 286
- Issue
- 29
- Pages
- 25922-25934
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3138264
- OpenAlex
- W2053024016
- Cited by
- 45
- References
- 58
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 2 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 4 · 2012: 5
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 645)
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- FA2H, sebaceous glands, sebum composition, sphingolipids, glucosylceramide, hair follicle morphogenesis, anagen, epidermal growth factor receptor, hair follicle homeostasis, skin barrier
- MeSH terms
- Fatty Acid Amide Hydrolases, Alopecia, Amidohydrolases, Animals, Epidermis, Hair, Male, Organ Specificity, Organ Size, Sebaceous Glands, Sebum, Sphingolipids, Gene Expression Regulation, Developmental, Transition Temperature, Cell Proliferation, Mice
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