Triacylglycerol‐Rich Oils of Marine Origin are Optimal Nutrients for Induction of Polyunsaturated Docosahexaenoic Acid Ester of Hydroxy Linoleic Acid (13‐DHAHLA) with Anti‐Inflammatory Properties in Mice

Abstract

Scope The docosahexaenoic acid ester of hydroxy linoleic acid (13‐DHAHLA) is a bioactive lipid with anti‐inflammatory properties from the family of fatty acid esters of hydroxy fatty acids (FAHFA). Methods and results To explore the biosynthesis of 13‐DHAHLA from dietary oils, C57BL/6N mice are gavaged for 8 days with various corn oil/marine oil mixtures containing the same amount of DHA. Plasma levels of omega‐3 FAHFAs are influenced by the lipid composition of the mixtures but do not reflect the changes in bioavailability of polyunsaturated fatty acids in plasma. Triacylglycerol‐bound DHA and linoleic acid serve as more effective precursors for 13‐DHAHLA synthesis than DHA bound in phospholipids or wax esters. Both 13(S)‐ and 13(R)‐DHAHLA inhibit antigen and PGE2‐induced chemotaxis and degranulation of mast cells to a comparable extent and 13(S)‐DHAHLA is identified as the predominant isomer in mouse adipose tissue. Conclusion Here, the optimal nutritional source of DHA is identified, which supports production of anti‐inflammatory FAHFAs, as triacylglycerol‐based marine oil and also reveals a possible role of triacylglycerols in the synthesis of FAHFA lipokines.

Insulin action in adipocytes, adipose remodeling, and systemic effects

“…Multiple additional FAHFAs are also biologically active and have anti-diabetic (Benlebna et al, 2020a) and anti-inflammatory effects (Kolar et al, 2019;Paluchova et al, 2020), as well as other beneficial effects such as improving cognition in obese mice (Wen et al, 2020). The abundance of PAHSA isomers is reduced in WAT and serum of AdChREBP knockout (KO) mice, and 9-PAHSA supplementation completely reverses their insulin resistance (Vijayakumar et al, 2017).…”

Analytical Methods for the Determination of Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) in Biological Samples, Plants and Foods

“…Surprisingly, both studied FAHFAs induced hepatic steatosis and fibrosis in some mice, which were more marked with 9-PAHPA. Again, in mice, dietary triacylglycerol-rich oils of marine origin were identified as optimal nutrients for the induction 13-DHAHLA exhibiting anti-inflammatory properties [38].…”

Effects of Early Sub-Therapeutic Antibiotic Administration and its Subsequent Withdrawal on Body Composition, Gut Microbiota and Metabolite Profiles in a Pig Model

“…FAHFAs are a novel class of bioactive lipid, forming by esteri cation hydroxyl group of a hydroxy fatty acid and the carboxyl group of a fatty acid [50]. Previous studies have shown that palmitic acid esters of hydroxy stearic acids and the family of polyunsaturated FAHFAs have antiin ammatory and immunomodulatory effects [51,52]. Besides, several new short-chain FAHFAs (SFAHFAs) of acetic acid or propanoic acid esteri ed long-chain hydroxy fatty acids tended to be lower in mice fed with a high-fat diet than those fed with a regular diet [53].Similarly, STA treatment decreased the concentrations of several SFAHFAs like FAHFA (2:0/24:2) and FAHFA (4:0/22:0) during the withdrawal period, which coincided with higher content of body lipid and lower abundance of Blautia, a bacterium with a protective role against obesity.…”