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Lipid Challenge Reveals Amplified Apolipoprotein Responses with Preserved Temporal Pattern in Polyendocrine Metabolic Ovarian Syndrome: An Exploratory Study

In brief

ApoA1 falls about fivefold during lipid stress in women with PMOS

In a crossover study of 12 women with polyendocrine metabolic ovarian syndrome and 10 controls, a 5-hour lipid infusion caused a fivefold drop in ApoA1 and a sustained reduction in ApoE isoforms in the PMOS group, with only partial rebound during a hyperinsulinemic clamp.

Journal
International journal of molecular sciences (Q1)
Published
25 July 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Ebrahim Rajab, Abu Saleh Md Moin, Manjula Nandakumar, Thozhukat Sathyapalan, Alexandra E Butler, Stephen L Atkin
PMID
42589314
DOI
10.3390/ijms27156656

Why clinicians should know about it

  • Picked for Biochemistry (medical) (top studies of the week, 16 August 2026): Lipid infusion reveals altered apolipoprotein dynamics in metabolic syndrome

Abstract

Acute elevation in circulating lipids induces reversible insulin resistance and alters triglyceride-rich lipoprotein flux. Whether insulin-regulated remodelling of high-density lipoprotein (HDL)-associated apolipoproteins is altered during defined lipid stress in women with polyendocrine metabolic ovarian syndrome (PMOS) remains unclear. In this exploratory, randomized, cross-over study, 10 healthy women and 12 women with PMOS underwent 5-h saline or lipid infusion, with a hyperinsulinemic-euglycemic clamp commencing at 180 min. Plasma proteomics were performed at baseline, 180 min and 300 min using linear modelling (limma). Lipid infusion induced the coordinated suppression of ApoA1 and ApoE isoforms at 180 min in both groups (FDR-adjusted p < 0.01), followed by partial recovery during hyperinsulinemia. Women with PMOS exhibited greater early suppression of ApoA1 (log2 fold-change -2.20, p = 0.001) and more persistent suppression of ApoE isoforms at 300 min (ApoE3 log2 -1.64, p = 0.001). ApoA1 suppression correlated inversely with NEFA exposure during lipid infusion (Spearman ρ = -0.54, p = 0.021). Controlled lipid challenge reveals amplified but reversible dysregulation of HDL-associated apolipoproteins in PMOS, with the preservation of the overall response pattern, but impaired recovery under hyperinsulinemic conditions. These findings suggest impaired adaptation to acute lipid stress in PMOS, with ApoA1 changes appearing to relate more closely to acute NEFA exposure than to clamp-derived insulin sensitivity.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.