• obesity

The Drosophila gene bmm was flagged in a genome-wide transcriptome profiling experiment screening for nutritionally regulated and evolutionarily conserved lipolysis effectors. This gene is orthologous to members of the mammalian PNPLA (patatin-like phospholipase-domain-containing) or ATGL (adipose triglyceride lipase) family, several of which play roles in triglyceride hydrolysis, energy metabolism, and lipid droplet homoeostasis. For Dmel\bmm, classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. There is an additional orthologous gene in flies, dob. The human gene PNPLA2 is implicated in a lipid-storage-related myopathy (MIM:609059).

A UAS construct of the wild-type human Hsap\PNPLA5 gene has been introduced into flies, but has not been characterized. None of the other human PNPLA genes has been introduced into flies.

Animals homozygous for loss-of-function mutations of bmm exhibit progressive obesity (measured as triacylglycerol content) during adulthood; they show incomplete storage-fat mobilization in response to starvation and resistance to starvation. Muscle function is also decreased, and fat accumulates in skeletal muscle. Chronic bmm overexpression depletes fat stores in a manner similar to that normally observed under conditions of food deprivation. Physical and genetic interactions for Dmel\bmm have been described; see below and in the gene report for bmm. Genetic interactions with Lsd-1 and Lsd-2 have been demonstrated; see FBhh0000497.

In Drosophila, lipolysis is under the control of multiple systems. In addition to the bmm-based pathway, a adipokinetic hormone signaling pathway regulates storage-fat accumulation and mobilization. Inactivation of components of the adipokinetic pathway also generates flies with excessive fat accumulation and limited fat-mobilization capability (see FBhh0000976). Phenotypes are additive: simultaneous loss of bmm and the adipokinetic receptor (AkhR) causes extreme obesity and blocks acute storage fat mobilization, even when food-deprived. Similarly, loss of both bmm and sphingolipid metabolism pathway member Sk2 (see FBhh0000977 for obesity phenotypes associated with defective sphingolipid metabolism) causes more muscle dysfunction than either mutant alone.

[updated Apr. 2020 by FlyBase; FBrf0222196]