Branched and linear fatty acid esters of hydroxy fatty acids (FAHFA) relevant to human health

0556127 - FGÚ 2023 RIV GB eng J - Journal Article
Riečan, Martin - Palůchová, Veronika - Lopes, Magno - Brejchová, Kristýna - Kuda, Ondřej
Branched and linear fatty acid esters of hydroxy fatty acids (FAHFA) relevant to human health.
Pharmacology and Therapeutics. Roč. 231, Mar (2022), č. článku 107972. ISSN 0163-7258. E-ISSN 1879-016X
R&D Projects: GA MŠMT(CZ) LTAUSA18104
Grant - others:AV ČR(CZ) LQ200111901
Program: Prémie Lumina quaeruntur
Institutional support: RVO:67985823
Keywords : FAHFA * OAHFA * PAHSA * meibum * cytochrome P450 * inhibitors
OECD category: Biochemistry and molecular biology
Impact factor: 13.5, year: 2022
Method of publishing: Limited access
https://doi.org/10.1016/j.pharmthera.2021.107972

Fatty acid esters of hydroxy fatty acids (FAHFAs) represent a complex lipid class that contains both signaling mediators and structural components of lipid biofilms in humans. The majority of endogenous FAHFAs share a common chemical architecture, characterized by an estolide bond that links the hydroxy fatty acid (HFA) backbone and the fatty acid (FA). Two structurally and functionally distinct FAHFA superfamilies are recognized based on the position of the estolide bond: omega-FAHFAs and in-chain branched FAHFAs. The existing variety of possible HFAs and FAs combined with the position of the estolide bond generates a vast quantity of unique structures identified in FAHFA families. In this review, we discuss the anti-diabetic and anti-inflammatory effects of branched FAHFAs and the role of omega-FAHFA-derived lipids as surfactants in the tear film lipid layer and dry eye disease. To emphasize potential pharmacological targets, we recapitulate the biosynthesis of the HFA backbone within the superfamilies together with the degradation pathways and the FAHFA regioisomer distribution in human and mouse adipose tissue. We propose a theoretical involvement of cytochrome P450 enzymes in the generation and degradation of saturated HFA backbones and present an overview of small-molecule inhibitors used in FAHFA research. The FAHFA lipid class is huge and largely unexplored. Besides the unknown biological effects of individual FAHFAs, also the enigmatic enzymatic machinery behind their synthesis could provide new therapeutic approaches for inflammatory metabolic or eye diseases. Therefore, understanding the mechanisms of (FA)HFA synthesis at the molecular level should be the next step in FAHFA research.
Permanent Link: http://hdl.handle.net/11104/0330479