The adipocyte-specific proteome

Transcriptome analysis shows that 62% (n=12510) of all human proteins (n=20162) are detected in adipocytes and 485 of these genes show an elevated expression in any adipocytes compared to other cell type groups. In-depth analysis of the elevated genes in adipocytes using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in adipocytes.

The adipocyte transcriptome

The scRNA-seq-based adipocyte transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in adipocytes compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:

• Cell type enriched: At least four-fold higher mRNA level in a certain cell type compared to any other cell type.
• Group enriched: At least four-fold higher average mRNA level in a group of 2-10 cell types compared to any other cell type.
• Cell type enhanced: At least four-fold higher mRNA level in a cell certain cell type compared to the average level in all other cell types.

Table 1. Number of genes in the subdivided specificity categories of elevated expression in the analyzed adipocyte types.

Adipocytes

As shown in Table 1, 485 genes are elevated in adipocytes compared to other cell types. Adipocytes are responsible for the storage of lipids in their lipid droplet. Examples of genes involved in this are FABP4 a lipid transporter and LIPE a lipase able to hydrolyze a broad number of different substrates.

FABP4 - adipose tissue
FABP4 - adipose tissue
FABP4 - adipose tissue

LIPE - adipose tissue
LIPE - adipose tissue
LIPE - adipose tissue

Adipocyte function

Adipose cells are mainly localized in adipose tissue as well as other loose connective tissues present under the skin and around the organs where it functions as a physical protective cushion. Protecting the underlying tissues is not the only function of adipose cells as these are also known to store lipids as well as have an endocrine function. Adipocytes take up and store lipids as triglyceride-rich lipoproteins in a lipid droplet which can be consumed during periods of low energy, effectively functioning as a battery for the body. The endocrine function of adipose cells is their secretion of adipokines like leptin, resistin, and adiponectin important for regulating lipid metabolism, insulin sensitivity, and the immune system. Dysregulation of this endocrine function, for example due to obesity, is linked to cardiovascular disorders, insulin resistance, and chronic inflammation.

The histology of organs that contain adipocytes, including interactive images, is described in the Protein Atlas Histology Dictionary.

Background

Here, the protein-coding genes expressed in adipocytes are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in different adipocyte types.

The transcript profiling was based on publicly available genome-wide expression data from scRNA-seq experiments covering 29 tissues and peripheral blood mononuclear cells (PBMCs). All datasets (unfiltered read counts of cells) were clustered separately using louvain clustering, resulting in a total of 557 different cell type clusters. The clusters were then manually annotated based on a survey of known tissue and cell type-specific markers. The scRNA-seq data from each cluster of cells was aggregated to mean normalized protein-coding transcripts per million (nTPM) and the normalized expression value (nTPM) across all protein-coding genes. A specificity and distribution classification was performed to determine the number of genes elevated in these single cell types, and the number of genes detected in one, several or all cell types, respectively.

It should be noted that since the analysis was limited to datasets from 29 tissues and PBMC only, not all human cell types are represented. Furthermore, some cell types are present only in low amounts, or identified only in mixed cell clusters, which may affect the results and bias the cell type specificity.

Relevant links and publications

Uhlén M et al., Tissue-based map of the human proteome. Science (2015)
PubMed: 25613900 DOI: 10.1126/science.1260419

Fagerberg L et al., Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. (2014)
PubMed: 24309898 DOI: 10.1074/mcp.M113.035600

Yu NY et al., Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium. Nucleic Acids Res. (2015)
PubMed: 26117540 DOI: 10.1093/nar/gkv608

Hildreth AD et al., Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat Immunol. (2021)
PubMed: 33907320 DOI: 10.1038/s41590-021-00922-4

Mardinoglu A et al., Defining the human adipose tissue proteome to reveal metabolic alterations in obesity. J Proteome Res. (2014)
PubMed: 25219818 DOI: 10.1021/pr500586e

Ouchi N et al., Adipokines in inflammation and metabolic disease. Nat Rev Immunol. (2011)
PubMed: 21252989 DOI: 10.1038/nri2921