Make or break - PEDS1 and AGMO orchestrate ether lipid homeostasis in human adipocytes and are associated with blood lipid profiles.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

BACKGROUND: Obesity and its associated sequelae have become a major global health concern. While ester-linked lipids are well-established regulators of adipocyte function and energy storage. Emerging evidence from cohort studies suggests that ether-linked lipid levels are also altered during the development of acquired obesity. The genes of two extra-peroxisomal enzymes of ether lipid metabolism, alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1), have recently been identified, but their physiological roles in humans remain poorly understood. METHODS: We conducted a monocentric, cross-sectional study analyzing subcutaneous adipose tissue from 30 patients undergoing abdominoplasty. To dissect the function of AGMO and PEDS1, we combined in vitro knockdown experiments in adipocyte-derived stem cells with pulse-chase tracing of a labeled ether lipid precursor. Untargeted lipidomics using liquid chromatography–tandem mass spectrometry was applied to in vivo differentiated adipocytes to assess the impact of AGMO activity on phospholipid composition. To explore a systemic relevance for AGMO and PEDS1 in humans, enzyme activity and gene expression data were correlated with blood lipid and metabolic parameters. RESULTS: We demonstrate that AGMO and PEDS1 are critical regulators of ether lipid subclass balance during adipocyte differentiation. Both enzymes ma

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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