What model organisms and interactomics can reveal about the genetics of human obesity

• Published in: Cellular and molecular life sciences : CMLS 2012-11, Vol.69 (22), p.3819-3834
• Main Authors: Williams, Michael J., Almén, Markus S., Fredriksson, Robert, Schiöth, Helgi B.
• Format: Article
• Language: English
• Subjects: Animals; AP-2 protein; Biochemistry; Biomedical and Life Sciences; Biomedicine; Body Mass Index; Body weight; Body Weight - genetics; Brain-derived neurotrophic factor; C. elegans; Caenorhabditis elegans - genetics; Cell Biology; Drosophila; Drosophila melanogaster - genetics; Drug discovery; Gene expression; Genetic Predisposition to Disease; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomics; Genotype; Humans; Insulin - biosynthesis; Insulin - metabolism; Insulin Secretion; Interactomics; Life Sciences; Melanocortin MC4 receptors; Mice; Models, Animal; Molecular modelling; Obesity; Obesity - genetics; Obesity - metabolism; Proopiomelanocortin; Proteins; Review; Signal Transduction; Signalling cascade genes; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-012-1022-5

Genome-wide association studies have identified a number of genes associated with human body weight. While some of these genes are large fields within obesity research, such as MC4R , POMC , FTO and BDNF , the majority do not have a clearly defined functional role explaining why they may affect body weight. Here, we searched biological databases and discovered 33 additional genes associated with human obesity ( CADM2 , GIPR , GPCR5B , LRP1B , NEGR1 , NRXN3 , SH2B1 , FANCL , GNPDA2 , HMGCR , MAP2K5 , NUDT3 , PRKD1 , QPCTL , TNNI3K , MTCH2 , DNAJC27 , SLC39A8 , MTIF3 , RPL27A , SEC16B , ETV5 , HMGA1 , TFAP2B , TUB , ZNF608 , FAIM2 , KCTD15 , LINGO2 , POC5 , PTBP2 , TMEM18 , TMEM160 ). We find that the majority have orthologues in distant species, such as D. melanogaster and C. elegans , suggesting that they are important for the biology of most bilateral species. Intriguingly, signalling cascade genes and transcription factors are enriched among these obesity genes, and several of the genes show properties that could be useful for potential drug discovery. In this review, we demonstrate how information from several distant model species, interactomics and signalling pathway analysis represents an important way to better understand the functional diversity of the surprisingly high number of molecules that seem to be important for human obesity.