In mice, the MED13 ortholog has been implicated in susceptibility to obesity (pubmed:22541436). The MED13 protein is a subunit of the Mediator complex; it is thought to a component of a sub-complex that can negatively regulate activation by the Mediator complex. There is a single ortholog in Drosophila, skd, for which loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\skd is also orthologous to a second very similar gene in human, MED13L.
Neither human gene has been introduced into flies.
Animals homozygous for loss-of-function alleles of Dmel\skd die prior to adulthood, typically at the larval-pupal transition. Animals in which RNAi directed against skd is targeted by muscle-specific drivers survive, but exhibit a progressive increase in total triglyceride content, an increase in adult abdominal fat body, and enlarged lipid droplets in fat body cells; they also exhibit increased resistance to starvation. Knock-down using a heart-specific driver evokes comparable obesity phenotypes. Physical and genetics interactions have been described for Dmel\skd; see below and in the gene report for skd.
Knockdowns of tested members of the wingless signaling pathway also result in obesity-related phenotypes; see the human disease model 'obesity, susceptibility to (postulated), Wnt signaling pathway' (FBhh0001102). Genetic experiments have been performed to assess epistatic relationships between wg and skd for the obesity-related phenotypes. These data support the conclusion that muscle-secreted wg protein acts as a downstream effector of skd function in muscle to suppress fat deposition in the fat body.
[updated Jul. 2019 by FlyBase; FBrf0222196]
Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death. (http://medical-dictionary.thefreedictionary.com/obesity).
The development of obesity is recognized as having both genetic and environmental components (https://www.sciencelearn.org.nz/resources/203-obesity-genetic-or-environmental).
The protein products of MED13 and MED13L are subunits of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase-II-transcribed genes. The MED13 protein is proposed to form a sub-complex with MED12, cyclin C, and CDK8 that can negatively regulate transactivation by mediator. [from Gene Cards, MED13, MED13L; 2017.02.27]
Many to one (2 human to 1 Drosophila); the second human gene is MED13.
Many to one (2 human to 1 Drosophila); the second human gene is MED13L.
High-scoring ortholog of human MED13 and moderate-scoring ortholog of MED13L (1 Drosophila to 2 human). Dmel\skd shares 27% identity and 40% similarity with the human genes.
