Pharmacoproteomics of Obesity: Definitions, Role and a Case Study of Dynamics of Human Plasma Proteome

Abstract

In this article, several definitions of pharmaco­ proteomics and why pharmacoproteomics are important for obesity studies are discussed. This illustrates with recent results on the dynamics of plasma proteome during leptin replacement therapy in genetically based leptin deficiency. Pharmacoproteomics belongs to the third generation of the ‘omics sciences. The first gen­ eration is represented solely by genomics, while the second includes proteomics and 21 other ‘omes’, as reflected in the OMES Table [101]. The term pharmacoproteomics is relatively new: it is still absent in the Oxford English Dictionary, which recognizes pharmacogenomics as “a branch of genomics dealing with the identifica­ tion of genes involved in individual responses to drugs”. A Scopus search for “pharmacopro­ teomics” returned 59 papers (the earliest pub­ lished in 1999 [1]) and a PubMed search resulted in 43 papers. Interestingly, the Future Medicine Group recognized the importance of pharmaco­ proteomics early, which was mentioned in at least 18 publications in the group’s journals and in five papers published in Pharmacogenomics, including [2,3]. As is usually the case with new terms, the defi­ nition of pharmacoproteomics is not yet carved in stone. The president of the Human Proteome Organization wrote: “Pharmacoproteomics, a term that is a synthesis of ‘pharmacology’ and ‘proteomics’, refers to the comprehensive pro­ teomics ana lysis that is relevant to the novel drug target discovery, drug metabolism, as well as drug efficacy and toxicity” [4]. Valdes et al. emphasized the role of pharmacoproteomics by noting that “variation in drug response is likely due to functional d ifferences in critical pro­ teins (absence, presence or modification of pro­ teins) that influence the efficacy of the net drug response” and that “proteome related studies