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FB2026_01
,
released March 12, 2026
The Drosophila SNAIL TF genes snail (sna), escargot (esg) and worniu (wor) have been used to characterize the role of this family of transcription factors in the regulation of lipid homeostasis, specifically their role in cardiomyocyte regulation of systemic lipid levels. The three paralogous Drosophila genes are orthologous to human paralogs SNAI2, SNAI1, and SNAI3.
None of the human genes (SNAI2, SNAI1, SNAI3) has been introduced into flies.
Overexpression of each of the three Drosophila SNAIL TF genes specifically in the heart promotes whole-body leanness (lower systemic levels of triglycerides) whereas their knockdown in the heart promotes obesity (higher systemic levels of triglycerides). Alterations in lipogenesis and lipolysis gene expression, mitochondrial biogenesis and respiration, and lipid storage droplet levels in the fat body are observed. Cardiac-specific alterations of the SNAIL TF levels do not perturb cardiac morphology, viability, lipid metabolism or fly food intake. Modifications of SNAIL TF levels in the fat body or intestine do not affect systemic lipid levels.
These results add to growing evidence that cardiomyocytes play an important role in the regulation of systemic lipid homeostasis; see also human disease models 'obesity and cardiomyocyte regulation of systemic lipid levels, MTTP-related' (FBhh0001197); 'obesity and cardiomyocyte regulation of systemic lipid levels, APOB-related' (FBhh0001198);'obesity, susceptibility to (postulated), MED13-related' (FBhh0000506); 'obesity, susceptibility to (postulated), MED12-related' (FBhh0000507).
[updated Feb. 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).
There is growing evidence that cardiomyocytes play an important role in the regulation of systemic lipid homeostasis (FBrf0234631, FBrf0244152, and references cited therein).
The adult mammalian heart has the ability to switch energy sources as dictated by substrate availability, hormonal status, and physiological conditions. Sixty to 90% of the energy used by the adult fasting heart is provided by the mitochondrial oxidation of long-chain fatty acids (FAs), with the remainder supplied by oxidation of glucose, lactate and ketone bodies. (Pascual and Coleman, 2016; pubmed:26993579)
SNAI1, SNAI2, and SNAI3 encode members of the SNAIL family of C2H2-type zinc finger transcription factors, which play critical roles in multiple early developmental processes, including mesoderm formation, induction of the epithelial to mesenchymal transition, and neural tube formation. [Gene Cards, SNAI1, SNAI2, SNAI3; 2020.02.14]
Low- to moderate-scoring ortholog of human SNAI1, SNAI2, and SNAI3 (multiple genes in both species).
Moderate-scoring ortholog of human SNAI1, SNAI2, and SNAI3 (multiple genes in both species).
Moderate- to high-scoring ortholog of human SNAI1, SNAI2, and SNAI3 (multiple genes in both species).