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Fiber Type and Subcellular-Specific Analysis of Lipid Droplet Content in Skeletal Muscle

Fiber Type and Subcellular-Specific Analysis of Lipid Droplet Content in Skeletal Muscle

Published on: June 8, 2022

Muscle and Liver Insulin Resistance Are Associated with Distinct Plasma Protein Profiles: Data from the DiOGenes

Esther J Kemper¹, Ellen E Blaak¹, Michiel E Adriaens²

¹Department of Human Biology, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, 6200 MD Maastricht, The Netherlands.

The Journal of Clinical Endocrinology and Metabolism

|October 10, 2025

Abstract

Context:

Insulin resistance (IR) can develop in multiple organs, representing distinct etiologies toward cardiometabolic disease.

Objective:

This study aimed to investigate which proteins and pathways are specific for liver IR or muscle IR in individuals with overweight or obesity of the Diet, Obesity, and Genes cohort (n = 535) (NCT00390637, ClinicalTrials.gov).

Methods:

First, independent associations between muscle and liver IR and protein abundance levels were assessed. In the analysis, we corrected for study center, sex, body mass index, and age, whereby the analyses on liver IR were adjusted for muscle IR and vice versa. Differentially abundant proteins were then subjected to pathway enrichment analysis.

Results:

Muscle IR was associated with 160 proteins, and liver IR was associated with 81 proteins. Of these, 12 were shared between both forms of IR. Pathway enrichment analysis identified 51 enriched pathways for muscle IR, characterized by a strong inflammatory profile, including chemokine signaling, interleukin-6 signaling, and complement system-related pathways. In contrast, liver IR was associated with 11 enriched pathways, primarily related to the complement system.

Conclusion:

Understanding the processes underlying these distinct IR phenotypes could inform the development of personalized prevention strategies.

Keywords:

liver obesity pathway enrichment analysis proteomics skeletal muscle tissue-specific insulin resistance

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