Z-Isomer Astaxanthins Exhibit Superior Anti-Obesity Effects in C. elegans

Xie J, Cai R, Hou X, Zhao K, Xiao J, Cao Y, Liu X. Z-Astaxanthin exhibits superior anti-obesity effects in Caenorhabditis elegans: insights from geometric isomers and signaling pathways. J Sci Food Agric 2025;105(9):4795-4807. doi: 10.1002/jsfa.14202.

Background: Astaxanthin (AST) is a carotenoid found in aquatic organisms that exists in both all-E and Z isomeric forms. The Z isomers have been reported to exhibit stronger antioxidant and biological activity than the all-E form. Although all-E AST is known for its anti-obesity potential, the effects of its Z isomers have not been fully clarified. This study therefore investigated whether Z AST exhibits superior lipid-lowering and anti-obesity effects compared with all-E AST using Caenorhabditis elegans as a model organism.

Hypothesis: This study hypothesized that Z isomers of astaxanthin, particularly 9-Z and 13-Z AST, would exert stronger anti-obesity effects than the all-E form by modulating lipid metabolism and energy balance through distinct molecular pathways.

Methods: The authors used synchronized C. elegans cultured under normal and high-fat conditions, treating them with all-E, 9-Z or 13-Z AST (60 μM). Lipid accumulation was visualized using oil red O staining, triglycerides were quantified and fatty acid composition was analyzed by GC–MS. Food intake and locomotion were recorded using the WormLab Imaging System, and locomotion speed was quantified with WormLab. Gene expression of key lipid and energy-regulating pathways was assessed by qPCR and fluorescence imaging in wild-type and mutant nematodes.

Results: Z AST, especially 9-Z, significantly reduced total fat and triglyceride levels by 41.2% and decreased large lipid droplets by up to 85.5%. The ratio of oleic to stearic acid (C18:1Δ9/C18:0) fell by 60–73%. Z isomers enhanced locomotion, reduced food intake and more effectively downregulated sbp-1, mdt-15, daf-2, daf-16, fat-6, and fat-7 than all-E AST.

Conclusions: Z-isomer astaxanthins exhibited markedly superior anti-obesity effects by suppressing lipid synthesis and promoting energy expenditure via sbp-1/mdt-15 and insulin signaling pathways. These findings highlight Z AST’s potential as an optimized bioactive compound for obesity prevention.