Variant-to-function approaches for adipose tissue: Insights into cardiometabolic disorders

Figures

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  Figure 1. A map of adipocyte biology The figure displays key aspects of adipocyte biology for maintaining adipose tissue function and metabolic health: transcriptional regulation of genes within the nucleus, storage and mobilization of lipids in and out of the adipocytes (lipid turnover), the secretory function of adipocytes, the role of extracellular matrix in the regulation of cell function and behavior, and the interaction of adipocytes with other cell types within adipose tissue.

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  Figure 2. The variant-to-function framework for adipose tissue biology This figure outlines the main steps in the variant-to-function framework for studying the functional consequences of genetic variants in adipose tissue. These steps include selecting a GWAS locus pertinent for adipose tissue, identifying the causal variant, identifying the effector gene, determining the relevant cell type and state, performing functional experiments to assess the effects on cellular function, and linking these cellular consequences to physiological mechanisms.

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  Figure 3. Screening natural genetic variation using a GWAS-in-a-dish approach The figure illustrates the GWAS-in-a-dish approach, where adipose tissue-derived stem cells or pre-adipocytes from a genetically heterogeneous population are cultured either in mixed villages (left) or in separate monocultures (right) and then differentiated into adipocytes. By combining donor genotypes with cellular phenotypes, this approach enables GWAS analysis to identify genetic loci associated with various cellular readouts. This facilitates linking natural genetic variation to cellular functions relevant for cardiometabolic disease outcomes.