Modulation of Δ5- and Δ6-desaturases in the brain-liver axis

Nutrition. 2024 Nov 12:131:112629. doi: 10.1016/j.nut.2024.112629. Online ahead of print.

Abstract

Objective: Obesity is associated with liver depletion of ω-3 polyunsaturated fatty acids (ω-3 PUFAS) promoting steatosis and inflammation, whose levels are maintained by diet or biosynthesis involving Δ-5D, Δ-6D desaturases and elongases.

Method: We aimed to assess Δ-5D and Δ-6D activities in liver and brain from mice fed a control diet (CD) or high-fat diet (HFD) for four to sixteen weeks.

Results: HFD led to (1) an early (4 weeks) enhancement in liver Δ-5D, Δ-6D, and PPAR-α activities, without changes in oxidative stress, liver damage or fat accumulation; (2) a latter progressive loss in hepatic desaturation with insufficient compensatory increases in mRNA and protein expression, leading to ω-3 PUFA depletion, PPAR-α down-regulation reducing FA oxidation, and liver steatosis with enhancement in lipogenesis; and (3) brain ω-3 PUFA depletion after 12 to 16 weeks of HFD feeding.

Conclusion: In conclusion, the brain-liver axis is drastically affected by obesity in a time dependent fashion.

Keywords: Antioxidant; Brain-liver axis; Metabolic dysfunction-associated fatty liver disease (MAFLD); Obesity; Reactive oxygen species (ROS); Δ-5D and Δ-6D desaturases.