Members of the family of perilipin genes are postulated to contribute to susceptibility to obesity in humans. These proteins are associated with the surface of lipid droplets and participate in lipid homeostasis by controlling deposition and mobilization of fats into and out of the lipid droplets. There are five perilipin genes in human (PLIN1-PLIN5); PLIN1 is implicated in the disease familial partial lipodystrophy type 4 (FPLD4, MIM:613877). There are two orthologous genes in Drosophila, Lsd-1 and Lsd-2. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both Drosophila genes.
A UAS construct of the wild-type human Hsap\PLIN1 gene has been introduced into flies. Expression of this human gene in the fly fat body results in localization of the Hsap\PLIN1 protein to fat body lipid droplets, but fails to rescue the giant lipid droplet larval phenotype and adult obesity phenotypes of Lsd-1 loss-of-function mutant animals. A UAS construct of the wild-type human Hsap\PLIN3 gene has also been introduced into flies, but has not been characterized.
Animals homozygous for loss-of-function mutations of Lsd-1 develop into obese but otherwise normal-looking adults (obesity assayed as triglyceride content per animal); they exhibit increased resistance to starvation. In the larval stage, fat body cells of Lsd-1 mutant animals exhibit a giant lipid droplet phenotype. Lsd-2 mutant animals exhibit the opposite phenotype, with less storage fat than control flies; Lsd-2 overexpression results in extra fat accumulation. Animals mutant for both fly genes have reduced body fat stores at eclosion, but recover as they age. Under a starvation/refeeding regime, the double mutant flies show both attenuated lipid mobilization and reaccumulation compared to control flies.
A fly model of age-dependent ectopic fat accumulation has been developed (see FBhh0000707). Loss of Dmel\HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced longevity on a high-fat diet. Transition to EFA appears to depend on regulation of Lsd-2 by HDAC6.
Genetic and physical interactions have been described for Lsd-1, Lsd-2 and HDAC6; see the below and in the relevant gene reports. Genetic interactions of Lsd-1 and Lsd-2 with bmm have been demonstrated; see FBhh0000504.
[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).
Members of the perilipin (PLIN) family are associated with the lipid droplet surface and are modulators of lipid metabolism in adipose and other tissues. PLIN3 has an additional role in mannose 6-phosphate receptor recycling between endosomes and the Golgi complex. [from Gene Cards, PLIN1, PLIN2, PLIN3; 2017.02.17]
Many to many (5 human to 2 Drosophila); other human genes are PLIN1, PLIN2, PLIN3, and PLIN4.
Many to many (5 human to 2 Drosophila); other human genes are PLIN2, PLIN3, PLIN4, and PLIN5.
Many to many (5 human to 2 Drosophila); other human genes are PLIN1, PLIN3, PLIN4, and PLIN5.
Many to many (5 human to 2 Drosophila); other human genes are PLIN1, PLIN2, PLIN4, and PLIN5.
Many to many (5 human to 2 Drosophila); other human genes are PLIN1, PLIN2, PLIN3, and PLIN5.
Low-to moderate-scoring ortholog of human PLIN1 and PLIN3; lower-scoring ortholog of PLIN2, PLIN5 and PLIN4 (2 Drosophila to 5 human); Dmel\Lsd-1 shares 19-21% identity and 36-39% similarity with human PLIN1 and PLIN3.
Moderate-scoring ortholog of human PLIN1 and PLIN2; lower-scoring ortholog of PLIN3, PLIN5 and PLIN4 (2 Drosophila to 5 human); Dmel\Lsd-2 shares 20-25% identity and 41% similarity with human PLIN1 and PLIN2.
