The Drosophila gene Stim was identified in an RNAi screen for genes that affected body fat content when knocked down. This gene is orthologous to human genes STIM1, which senses calcium in the ER lumen and signal to other proteins when ER calcium is depleted, as part of SOCE (store-operated calcium entry). For Dmel\Stim, an amorphic allele, EMS-induced mutant alleles, and several RNAi targeting constructs have been generated. The human gene STIM1 has been associated with Stormorken syndrome (MIM:185070), tubular aggregate myopathy 1 (MIM:160565), and immunodeficiency 10 (MIM:612783).
Knockdown of Stim or other SOCE genes in the Drosophila fat body causes a large increase (more than double) in total body fat content, which accumulates as subcuticular body fat. Overexpression of Stim depletes subcuticular lipid stores and reduces body fat content. Stim knockdown does not affect carbohydrate metabolism. Lack of Stim is proposed to cause hyperphagia (overeating), as limiting food intake prevents fat accumulation. A single pulse of anti-Stim RNAi in adults causes progressive accumulation of body fat for the next three weeks. By that age, flies also show an increased abdominal circumference, hyperglycemia, impaired climbing ability, and decreased lifespan. Simultaneous knockdown of Stim and NPF, a neuropeptide similar to vertebrate neuropeptide Y that is known to regulate food intake, also reduced fat accumulation compared to Stim knockdown alone. Stim knockdown might also affect body fat content by promoting the secretion of adipokinetic hormone, which controls fat storage and accumulation (see FBhh0000976).
Several UAS constructs of the human Hsap\STIM1 gene have been introduced into flies, including wild-type and genes carrying modifications of regulatory phosphorylation sites. Regulation of phosphorylation of Hsap\STIM1 has been investigated in flies in the context of signaling pathways regulated by exercise.
[updated Apr. 2020 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 established functions of STIM proteins are sensing calcium in the ER lumen and communicating store depletion to other proteins, including ORAI, in the plasma membrane. A simple demonstration of calcium sensing is that mutations in the calcium-binding domain of STIM1 that lower its affinity for calcium result in a movement of STIM to ER-plasma membrane junctions, resembling that elicited by store depletion and in constitutive calcium influx. (Adapted from Hogan and Rao 2015, pubmed:25998732. See Baumbach et al., FBrf0224024 for a description of this process in Drosophila.)
One to one: one human gene to one Drosophila gene.
Many to one: two human genes to one Drosophila gene.
No orthologs identified by standard algorithms; literature supports orthology of human NPY and Dmel\NPF.
