Potential physio-pathological effects of branched fatty acid esters of hydroxy fatty acids

Abstract

Branched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) are a new endogenous lipid class with recently uncovered interesting biological effects and which have been detected in food of plant and animal origins. Some FAHFAs can improve glucose tolerance and insulin sensitivity, stimulate insulin secretion, and exert anti-inflammatory effects. Other beneficial health effects have also been suggested, in particular against some cancers. FAHFAs could therefore be a potential therapeutic target for the treatment of numerous metabolic disorders such as type II diabetes, hepatic steatosis, cardiovascular diseases and various cancers. Their recent discovery has generated a great interest in the field of human health. This short review aims at bringing together the information available to date in the literature concerning their chemical synthesis, biosynthesis and degradation pathways as well as their potential physio-pathological beneficial effects. Contents

Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2

“…FAHFAs are recently discovered as endogenous lipid metabolites with multiple bioactivities such as anti-inflammatory [ 2 ], anti-diabetic [ 2 , 11 ], anti-apoptotic activities [ 3 ], and also promote browning of white adipose tissue [ 17 ]. Despite their structural diversity with more than 300 regioisomers [ 5 ], to date, the PAHSA family is the most studied [ 1 , 5 , 8 ]. The studies focusing on the effects of polyunsaturated FAHFAs such as ω-3 (DHALA and EPAHSA) and ω-6 (LAHLA) fatty acids are limited.…”

“…We assume that activation of NRF2 by 12-DHAHOA could be the cause for increased TAGs in C3A cells. Moreover, previous studies have also demonstrated the abundance of FAFHFA-TAGs over white adipose tissue and are believed to be an important reservoir of FAHFAs in cells and tissues [ 5 ]. They also reported that FAHFAs are incorporated into TAGs by the action of diacylglycerol acyltransferases DGAT1 and DGAT2 in adipocytes in vitro [ 22 ].…”

“…FAHFAs are reported to exhibit important biological properties such as antidiabetic, anti-inflammatory, anti-apoptotic, and antioxidant activities [ 2 , 3 , 4 ]. Several in vitro and in vivo studies demonstrated the FAHFAs de novo synthesis in mammals by the transferring a fatty acid from a fatty acid-CoA to a hydroxy fatty acid via lipid acyltransferases [ 5 ]. They are also present in dietary plant sources as well as animal meats.…”

“…In addition, FAHFAs are known to be the endogenous substrates for hydrolases such as ADTRP (androgen-dependent TFPI-regulating protein), AIG1 (androgen-induced gene 1 protein), and pancreatic lipase CEL (carboxy-ester lipase) [ 6 , 7 ]. The most studied FAHFAs are the palmitic-hydroxy stearic acid (PAHSA) with ester linkage at C 5 to C 13 [ 1 , 5 , 8 ]. PAHSAs augmented intestinal crypt Paneth cell bactericidal potency via GPR 120 and reduced the colonic T-cell activation and pro-inflammatory cytokine or chemokine expression [ 9 ].…”

Potential favourable health effects of some dietary uncommon fatty acids

“…It is important to note that these health effects of FAHFAs have been demonstrated with pharmacological doses in animal models or linked to circulating FAHFAs levels, but not associated to diet normal content. Several comprehensive reviews on branched FAHFAs have been recently published (Brejchova et al, 2020;Benlebna et al, 2021).…”