Lipidomics in MAFLD, NASH & Cardiovascular Research

Lipidomics in MAFLD, NASH & Cardiovascular Research

Creative Proteomics provides an end-to-end analytical platform for Lipidomics in MAFLD, NASH & Cardiovascular Research, delivering high-resolution quantification of complex lipid species within hepatic and vascular microenvironments. By integrating untargeted discovery with targeted absolute quantification, we enable researchers to map the lipid homeostasis mechanism and identify predictive biomarkers for metabolic associated fatty liver disease and atherosclerosis progression. Our workflows utilize advanced LC-MS/MS and MSI technologies to resolve isomeric complexity and ensure the highest data integrity for translational medicine, supporting drug target identification and mechanism-of-action studies.

Key capabilities

  • Isomeric Resolution: Advanced ion mobility (TIMS) and multi-stage fragmentation to distinguish pro-inflammatory and anti-inflammatory lipid isomers.
  • Comprehensive Lipid Coverage: Direct quantification of 50+ lipid classes including low-abundance oxysterols, sphingolipids, and bile acid conjugates.
  • Multi-Scale Insights: Seamless integration of systemic blood-based profiling with tissue-specific MALDI-MS imaging for spatial pathometabolism.
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  • Trends & Challenges
  • Integrated Solutions
  • Technical Advantages
  • Case Studies
  • FAQ

Translational Lipidomics Solution Matrix: From Discovery to Mechanism

To assist researchers in navigating the vast data landscape of metabolic diseases, Creative Proteomics has developed a context-triggered solution matrix. This framework aligns specific research objectives with optimized analytical services.

Serum Biomarker Discovery for NASH Progression

Situation & Goal

A clinical researcher needs to identify serum markers that can non-invasively differentiate patients with NASH from those with simple steatosis. The goal is broad lipidomic screening to build a multivariate diagnostic model.

Deliverables

Comprehensive differential lipid lists, VIP score plots, volcano plots, and pathway enrichment maps.

Plaque Microenvironment and Spatial Localization

Situation & Goal

A study into why certain atherosclerotic plaques rupture while others remain stable. The goal is mapping the in situ distribution of lipids within the plaque core and fibrous cap.

Deliverables

High-resolution ion images showing precise lipid localization within vascular tissue sections.

Gut-Liver Axis and Bile Acid Homeostasis

Situation & Goal

Investigating how gut microbiota changes impact the progression of liver fibrosis through bile acid signaling. The goal is absolute quantification of primary, secondary, and conjugated bile acids.

Deliverables

Quantitative data for 60+ bile acid species with detailed conjugation ratio analysis.

Mitochondrial Lipid Remodeling in Cardiomyocytes

Situation & Goal

Assessing organelle-level lipid changes in response to heart failure or diabetic cardiomyopathy. The goal is analysis of mitochondrial-specific lipids like cardiolipins and their oxidation states.

Deliverables

Detailed reports on acyl chain length and unsaturation indices of mitochondrial membrane lipids.

Adipogenesis and Systemic Lipid Signaling

Situation & Goal

Evaluating how fat tissue expansion alters the secretion of bioactive lipid mediators. The goal is profiling signaling lipids like steroids and sphingolipids during adipocyte differentiation.

Deliverables

Precise quantification of hormonal precursors and bioactive secondary messengers.

MoA Validation for Lipid-Lowering Therapies

Situation & Goal

Evaluating the off-target effects and metabolic normalization of a novel drug candidate. The goal is tracking dynamic shifts in the global lipidome pre- and post-treatment.

Deliverables

Comparative lipidomic response maps illustrating drug-induced metabolic shifts and efficacy.

Selected Case Studies

Client Publication: Felix, J. B., et al. (2025). Nature Metabolism. DOI: 10.1038/s42255-025-01334-6
Focus: Adipocyte-Derived Metabolites and Postprandial Thermogenesis.

Targeted Absolute Quantification for Endocrine Regulation

Research Goal

Research teams focused on obesity, energy balance, and endocrine regulation needed to understand the signaling role of adipocyte-derived metabolites.

Method Used

Targeted absolute quantification of mevalonate pathway metabolites in mouse adipose tissue using a Prominence UFLC HPLC system coupled to a 6500 QTRAP triple quadrupole mass spectrometer.

Result Obtained

The study demonstrated that adipocytes secrete N-acetylaspartate (NAA) in response to postprandial signals, which in turn regulates body temperature via thyroid hormone pathways.

Heatmap visualization for targeted lipid analysis in mouse adipose tissue for metabolic research.
Figure 1: Heatmap displaying differential concentrations of NAA and mevalonate pathway intermediates in brown versus white adipose tissue.
Client Publication: Dimovasili, C., et al. (2024). GeroScience. DOI: 10.1007/s11357-024-01353-3
Focus: White Matter Lipid Alterations in Primate Brain Aging.

Untargeted Profiling for Lipid Remodeling in Aging

Research Goal

Scientists exploring the systemic consequences of metabolic aging and tissue-specific lipid remodeling needed to evaluate shifts in the lipid homeostasis mechanism.

Method Used

LC-MS untargeted lipidomic profiling of brain white matter in rhesus monkeys across their lifespan.

Result Obtained

The research identified a significant age-related decline in ether-linked phospholipids, which are essential for membrane integrity and protection against oxidative stress.

UMAP plot illustrating lipidomic divergence in aging primates for metabolic research studies.
Figure 2: UMAP plot clustering rhesus monkey white matter samples based on comprehensive lipidomic profiles across biological age groups.

Frequently Asked Questions

How does lipidomics improve upon traditional AST/ALT testing for NASH?
Lipidomics identifies the specific accumulation of toxic lipid species, such as long-chain ceramides, which are directly involved in hepatocellular injury and fibrosis. Unlike traditional liver enzymes that reflect damage, lipidomics identifies the metabolic drivers of the disease.
What is the significance of ether-linked phospholipids in aging and metabolic health?
Ether-linked phospholipids, such as plasmalogens, act as endogenous antioxidants and are critical for membrane fluidity. Their decline is a hallmark of oxidative stress and is frequently observed in both metabolic aging and advanced cardiovascular disease.
Can your platform differentiate between double-bond positions in fatty acid chains?
Yes, by utilizing advanced ion mobility (TIMS) and specific fragmentation patterns, we can often resolve the double-bond position and sn-position on the glycerol backbone, providing structural clarity for cardiovascular lipid profiling.
What is the minimum sample requirement for a liver biopsy lipidomic study?
For liver tissue, we typically require 10–20 mg of fresh-frozen material. However, our high-sensitivity micro-extraction protocols can accommodate as little as 5 mg for specialized targeted panels.
How do you handle the high dynamic range of lipids in plasma?
We use specialized extraction methods and high-performance chromatography to separate high-abundance species like triacylglycerols from low-abundance signaling lipids, combined with mass spectrometers capable of wide dynamic ranges.
Is it possible to track the gut-liver axis through lipidomics?
Absolutely. By profiling bile acids and short-chain fatty acids in both portal blood and hepatic tissue, we can provide a detailed map of how gut microbiota-derived signals regulate hepatic lipid metabolism and fibrosis.
What spatial resolution can be achieved for vascular imaging?
Our MALDI-MSI system offers spatial resolutions down to 20 μm, allowing for the precise localization of lipids within atherosclerotic plaques.
How are internal standards used to ensure data quality?
We use a comprehensive suite of isotope-labeled lipid standards (one per lipid class) to normalize for extraction efficiency and matrix effects, ensuring absolute quantitative accuracy and batch-to-batch reproducibility.
* Our services can only be used for research purposes and Not for clinical use.

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