# Dysregulated high-density lipoprotein and low-density lipoprotein subfractions increase metabolic dysfunction-associated steatotic liver disease risk: a study of patients across body mass index categories

**Authors:** Hao-Yun Yu, Jia-Qi Zhang, Pei-Qi Sun, Qing-Hua Li, Hong Lin, Jia-Yang Wang, Xiao-Jing Qian, Xiao-Di Yang, Cheng Hu, Ping Tian, Yuan-Ye Jiang, Guo-Qiang Lin

PMC · DOI: 10.3389/fnut.2026.1737860 · Frontiers in Nutrition · 2026-02-13

## TL;DR

This study finds that different lipoprotein subfractions in lean and overweight individuals with liver disease could serve as biomarkers for diagnosis.

## Contribution

The study identifies unique lipoprotein subclasses in lean and overweight MASLD patients that could act as potential biomarkers.

## Key findings

- Lean MASLD patients had six unique lipoprotein subclasses with diagnostic accuracy (AUC > 0.7).
- Overweight MASLD patients had 13 unique lipoprotein subclasses with high diagnostic value.
- Lipoprotein subfractions correlated with clinical parameters like blood glucose and liver enzymes.

## Abstract

To investigate biomarker differences among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) across body mass index (BMI) types, we analyzed clinical data from 2,013 subjects and serum samples from 402 patients. The clinical characteristics and lipoprotein subclass profiles were evaluated.

Participants were grouped based on BMI into overweight MASLD (113 participants), overweight controls (107 participants), lean MASLD (83 participants), and lean controls (99 participants). Serum samples from each group underwent nuclear magnetic resonance-based metabolomic analyses, and clinical and omics data were compared between the lean and overweight MASLD groups and paired control cohorts.

Our study demonstrated distinct omics characteristics for lean MASLD compared with their overweight equivalents. Metabolomic analysis of the serum from the four groups identified six lipoprotein subclasses with significant diagnostic accuracy (area under the curve (AUC) > 0.7), unique to lean individuals with MASLD. In contrast, overweight patients with MASLD had 13 unique lipoprotein subclasses that exhibited a high diagnostic value. These lipoproteins correlate with clinical parameters, such as uric acid, urea, creatinine, eosinophils, blood glucose, and alanine aminotransferase.

Lean and overweight patients with MASLD display unique lipoprotein omics characteristics in an Asian population, primarily involving high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subcomponents, suggesting their potential as effective biomarkers.

## Linked entities

- **Diseases:** metabolic dysfunction-associated steatotic liver disease (MONDO:0013209), MASLD (MONDO:0013209)

## Full-text entities

- **Genes:** PMCH (pro-melanin concentrating hormone) [NCBI Gene 5367] {aka MCH, ppMCH}, H3C3 (H3 clustered histone 3) [NCBI Gene 8352] {aka H3.1, H3/c, H3FC, HIST1H3C}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, TPO (thyroid peroxidase) [NCBI Gene 7173] {aka MSA, TDH2A, TPX}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, LPL (lipoprotein lipase) [NCBI Gene 4023] {aka HDLCQ11, LIPD}, CYGB (cytoglobin) [NCBI Gene 114757] {aka HGB, NOD, STAP}, TSHR (thyroid stimulating hormone receptor) [NCBI Gene 7253] {aka CHNG1, LGR3, hTSHR-I}, TG (thyroglobulin) [NCBI Gene 7038] {aka AITD3, TGN}, BCHE (butyrylcholinesterase) [NCBI Gene 590] {aka BCHED, CHE1, CHE2, E1}, H2AC8 (H2A clustered histone 8) [NCBI Gene 3012] {aka H2A.1, H2A.2, H2A/a, H2AFA, HIST1H2AE}, CETP (cholesteryl ester transfer protein) [NCBI Gene 1071] {aka BPIFF, HDLCQ10}, ABCA1 (ATP binding cassette subfamily A member 1) [NCBI Gene 19] {aka ABC-1, ABC1, CERP, HDLCQTL13, HDLDT1, HPALP1}, APOB (apolipoprotein B) [NCBI Gene 338] {aka FCHL2, FLDB, LDLCQ4, apoB-100, apoB-48}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, APOA1 (apolipoprotein A1) [NCBI Gene 335] {aka AMYLD3, HPALP2, apo(a)}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}
- **Diseases:** Fatty Liver (MESH:D005234), obese (MESH:D009765), Overweight (MESH:D050177), metabolic dysregulation (MESH:D021081), Metabolic dysfunction (MESH:D008659), thyroid (MESH:D013966), CHE (MESH:C537417), hepatocyte injury (MESH:D014947), HL (MESH:C538324), MASLD (MESH:D008107), inflammation (MESH:D007249), cirrhosis (MESH:D005355), hyperlipidemia (MESH:D006949), metabolic syndrome (MESH:D024821), lipoprotein abnormalities (MESH:C563618), Dyslipidemia (MESH:D050171), Non alcoholic (MESH:D000437), diabetes (MESH:D003920), Tumor (MESH:D009369), liver fibrosis (MESH:D008103), CKD (MESH:D051436), type 2 diabetes (MESH:D003924), Alcoholic Liver Disease (MESH:D008108), lean (MESH:D013851), renal impairment (MESH:D007674), compromised liver function (MESH:D056486), coronary artery disease (MESH:D003324), liver injury (MESH:D017093), hepatocellular carcinoma (MESH:D006528), Hyperuricemia (MESH:D033461), hepatic lipid (MESH:D011017), hypertriglyceridemia (MESH:D015228), hypertension (MESH:D006973), disordered lipid metabolism (MESH:D052439), hyperinsulinemia (MESH:D006946), atherosclerosis (MESH:D050197), cardiovascular disease (MESH:D002318), IR (MESH:D007333)
- **Chemicals:** phospholipid (MESH:D010743), cholesterol (MESH:D002784), blood glucose (MESH:D001786), bilirubin (MESH:D001663), estradiol (MESH:D004958), UA (MESH:D014527), TG (MESH:D014280), Lipid (MESH:D008055), alcohol (MESH:D000438), T3 (MESH:D014284), glucose (MESH:D005947), Cr (MESH:D003404), Fasting blood glucose (-), T4 (MESH:D013974), urea (MESH:D014508), Lp(a) (MESH:D010649), PC (MESH:D010713)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** CA211 — Homo sapiens (Human), Transformed cell line (CVCL_U658)

## Full text

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## Figures

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## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12947705/full.md

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Source: https://tomesphere.com/paper/PMC12947705