The Transcriptome, Proteome, and Metabolome of Obesity

Obesity is a multifactorial metabolic disease with profound changes in the biomolecular composition and function of multiple organs and tissues. Omics technologies allow for the comprehensive characterization of a near-complete complement of genes, proteins, and metabolites, and have been applied quite extensively for understanding the molecular pathogenesis of obesity and for identifying markers of weight gain and weight loss. This chapter concentrates on transcriptomics-, proteomics-, and metabolomics-based observations about obesity, seen through the lens of profiling studies, tissue-specific omics, omics in special populations (e.g., non-Caucasian ethnicities, maternal and childhood obesity), and omics-based inquiries into obesity interventions. Within each omics platform, some common themes emerge for obesity-associated changes, along with findings restricted to more specialized settings. Broadly, the weight of evidence implicates gene and protein-level changes in pathways related to lipid metabolism, inflammatory signaling, mitochondrial function, and extracellular matrix remodeling in obesity. Metabolomics studies attest to frequently observed changes in branched-chain amino acid and aromatic amino acids, phospholipids and lysophospholipids, and bile acids and tryptophan/kynurenine metabolism, among others. A survey of the literature also illuminates limitations of technology, study designs, and scope within each omics platform and highlights areas of obesity research in need of more data and areas amenable to more sophisticated investigations in the future.