Control of triglyceride storage by a WD40/TPR‐domain protein

Abstract

Obesity is a metabolic disorder related to improper control of energy uptake and expenditure, which results in excessive accumulation of body fat. Initial insights into the genetic pathways that regulate energy metabolism have been provided by a discrete number of obesity-related genes that have been identified in mammals. Here, we report the identification of the adipose (adp) gene, the mutation of which causes obesity in Drosophila. Loss of adp activity promotes increased fat storage, which extends the lifespan of mutant flies under starvation conditions. By contrast, adp gain-of-function causes a specific reduction of the fat body in Drosophila. adp encodes an evolutionarily conserved WD40/tetratricopeptide-repeat-domain protein that is likely to represent an intermediate in a novel signalling pathway.

Proteomic insights into an expanded cellular role for cytoplasmic lipid droplets

“…Knockouts of CLD-related proteins for other species have also been reported, such as the Drosophila adipose gene ( adp ) ( 86 ), and the Drosophila PAT protein analog LSD2 ( 58,61 ).…”

Effect of Energy Restriction on Growth, Slaughter Performance,Serum Biochemical Parameters and Lpin2/WDTC1/mRNA Expressionof Broilers in the Later Phase

“…WDTC1 gene appears to inhibit fat formation in a dosage-sensitive manner (Suh et al, 2007). Loss of WDTC1 activity promotes increased fat storage and gain-of-function of WDTC1 causes a specific reduction of the fat body in Drosophila (Hader et al, 2003). WDTC1 Variants were found to be strongly associated with obesity too (Lai et al, 2009).…”

A comparative perspective on lipid storage in animals

“…Indeed, many conserved proteins discovered in invertebrates have been shown to exert similar functions in mammals. Adipose (adp) is one such evolutionary conserved gene, encoding a protein with a WD40 domain that regulates chromatin dynamics and gene transcription (Häder et al, 2003). adp was initially cloned from obese flies (Doane, 1960), and loss of its function promotes TAG storage in flies and worms, pointing to the crucial role this gene plays in energy homeostasis (Häder et al, 2003;Suh et al, 2007).…”

“…Adipose (adp) is one such evolutionary conserved gene, encoding a protein with a WD40 domain that regulates chromatin dynamics and gene transcription (Häder et al, 2003). adp was initially cloned from obese flies (Doane, 1960), and loss of its function promotes TAG storage in flies and worms, pointing to the crucial role this gene plays in energy homeostasis (Häder et al, 2003;Suh et al, 2007). Similar to in invertebrate models, mice that are heterozygous for Wdtc1, the homolog of adp, are obese and insulin resistant, which provides further support for a conserved role of this protein in modulating lipid accumulation (Suh et al, 2007).…”