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. 2025 Mar-Apr;51(2):e70017.
doi: 10.1002/biof.70017.

A novel peptide derived from Haematococcus pluvialis residue balanced lipid metabolism through NHR-49/PPARα and AAK-2/AMPK pathways in Caenorhabditis elegans

Liang Ke  1   2 , Wanshi He  1   2 , Chuyao Zong  1   2 , Tiantian Wang  1   2 , Jie Xiao  1   2 , Yong Cao  1   2 , Hang Xiao  3 , Xiaojuan Liu  1   2
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A novel peptide derived from Haematococcus pluvialis residue balanced lipid metabolism through NHR-49/PPARα and AAK-2/AMPK pathways in Caenorhabditis elegans

Liang Ke et al. Biofactors. 2025 Mar-Apr.

Abstract

To explore the potential value of Haematococcus pluvialis residue after astaxanthin extraction, a novel peptide (HPp) was identified as a bioactive component. However, the possible lipid-lowering effect in vivo remains unclear. Thus, the classic model of Caenorhabditis elegans (C. elegans) was employed to evaluate the anti-obesity effects and underlying mechanism. The results showed that 100 μM HPp significantly reduced the overall fat and triglyceride contents, while also remarkably decreasing the lipid droplets size and promoting desaturation of C18:0 to C18:1n9. Subsequent analysis indicated that HPp increased energy expenditure and alleviated intestinal distension. Further molecular research revealed that HPp activated the gene expression of fat-6, fat-7, nhr-49, acs-2, aak-2, atgl-1. Notably, the lipid-lowering effects were abolished in fat-6, fat-7, nhr-49 mutants, and further verified in GFP-tagged nematodes, indicating that HPp balanced lipid metabolism by activating NHR-49/PPARα and AAK-2/AMPK pathways in C. elegans. These findings highlight the high-value applications of marine microalgae.

Keywords: AAK‐2/AMPK; Caenorhabditis elegans; Haematococcus pluvialis peptide; NHR‐49/PPARα; anti‐obesity; lipid metabolism.

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