Lipidomics Revealed the Suppression of 5-PAHSA from Human Milk on Macrophage Foam Cell Formation

  • J Agric Food Chem. 2025 Oct 22;73(42):27089-27098. doi: 10.1021/acs.jafc.5c06907.
Yu Zhang  1 ,  Shuang Zhu  1 ,  Yuan He  1 ,  Jing-Nan Lei  1 ,  Hailong Wang  1 ,  Chinping Tan  2 ,  Yuan-Fa Liu  1 ,  Mingquan Chen  3 ,  Yong-Jiang Xu  1
Affiliations
  • 1. School of Food Science and Technology, State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, People's Republic of China.
  • 2. Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, UPM, Serdang, Selangor 43400, Malaysia.
  • 3. Department of Emergency, Huashan Hospital, Fudan University, Shanghai 200040, China.
PMID: 41061708 DOI: 10.1021/acs.jafc.5c06907
Abstract

Human milk contains bioactive lipids that provide long-term cardiovascular benefits, but the specific components and mechanisms remain unclear. This study aimed to identify lactation stage-specific lipid changes and assess the role of 5-palmitic acid ester of hydroxystearic acid (5-PAHSA) in macrophage foam cell formation. Nontargeted lipidomics across colostrum, transitional, and mature milk identified 189 significantly modulated lipids, with 5-PAHSA being 1.74-fold higher in colostrum than in mature milk (p < 0.0001). In an oxidized low-density lipoprotein-induced foam cell model, 5-PAHSA reduced intracellular lipid accumulation, decreased the Cholesterol ester/total Cholesterol ratio by 25% (p < 0.01), upregulated Cholesterol efflux/hydrolysis genes (ABCA1, ABCG1, nCEH), and downregulated uptake/esterification genes (CD36, SRA, ACAT1). Moreover, 5-PAHSA enhanced autophagic flux, possibly via the FOXO1/TFEB pathway, thereby suppressing macrophage foam cell formation. This study provides novel insights into lipid components and cardiovascular bioactivity of human milk throughout lactation.

Keywords
FAHFAs; FoxO1; TFEB; autophagy; foam cells; human milk; lipidomics.
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