In a genomic study of variants associated with obesity in humans, variants associated with the human gene DCHS1 were identified. DCHS1 encodes a calcium-dependent cell-cell adhesion molecule. There is a single orthologous gene in Drosophila, ds. Ubiquitous knockdown of ds, effected by RNAi, results in a significant increase in triacylglyceride (TAG) level, measured as the ratio of TAG to protein.
Dmel\ds is known to be a regulator of the Hippo signaling pathway. Additional genes involving in the Hippo signaling pathway were assessed in flies: Dmel\ft (orthologous to human FAT4); Dmel\fj (orthologou to human FJX1); Dmel\hpo (orthologous to human STK3 and STK4); ubiquitous knockdown of each of these genes results in a significant increase in triacylglyceride level. Results support the hypothesis that Hippo pathway activity in the nervous system regulates adiposity in Drosophila.
Using an independent cohort, an additional human gene, TAOK2, was implicated in development of obesity. The Drosophila ortholog, Tao is also a regulator of the Hippo signaling pathway. Ubiquitous knockdown of Tao, effected by RNAi, also results in a significant increase in triacylglyceride level.
A number of the related human genes have been introduced into flies, but have not been assessed in the context of this disease model: Hsap\FAT4, Hsap\STK3, Hsap\STK4, Hsap\TAOK2.
[updated Dec. 2021 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).
STK3 and STK4 encode serine/threonine protein kinases that are core components of the Hippo signaling pathway. [Gene Cards, STK3, STK4; 2021.12.15]
TAOK2 encodes a serine/threonine protein kinase that is involved in many different processes. [Gene Cards, TAOK2; 2021.12.15]
DCHS1 and FAT4 encode calcium-dependent cell-cell adhesion molecules of the cadherin family. [Gene Cards, DCHS1, FAT4; 2021.12.15]
The FJX1 gene is not well characterized in human. [Gene Cards, FJX1; 2021.12.15] The Drosophila gene fj has been shown to modulate activity of ft and ds (FBrf0205751, FBrf0210769).
Many to one: 2 human genes to 1 Drosophila gene.
One to one: 1 human gene to 1 Drosophila gene.
One to one: 1 human gene to 1 Drosophila gene.
Many to one: 2 human genes to 1 Drosophila gene
Many to one: 2 human genes to 1 Drosophila gene.
Many to one: 3 human genes to 1 Drosophila gene.
High-scoring ortholog of human DCHS1; moderate-scoring ortholog of DCHS2.
High-scoring ortholog of human FAT4.
High-scoring ortholog of human FJX1.
High-scoring ortholog of human STK3 and STK4.
Moderate- to high-scoring ortholog of human TAOK1, TAOK2, TAOK3.