Lipolysis is defined as the catabolism of triglycerides (triacylglycerols) stored in cellular lipid droplets. In Drosophila, lipolysis is under the control of multiple systems, one of which is an adipokinetic hormone Akh signaling pathway that regulates storage-fat accumulation and mobilization. In terms of its role in catabolism of triglycerides and lipid balance, Dmel\Akh is analogous to to mammalian peptide hormone glucagon. (In insects under normal dietary conditions, the role of AKH in carbohydrate metabolism may differ somewhat from that of glucagon in mammals.)
Inactivation of components of this pathway (adipokinetic hormone, Akh, or its receptor, AkhR) results in flies with excessive fat accumulation and limited fat-mobilization capability. Using loss-of-function mutations of AkhR, this system has been used to study metabolic changes in subsequent generations among F1 and F2 offspring of obese animals.
Amorphic mutations generated by targeted recombination and RNAi targeting constructs have been generated for Dmel\Akh; RNAi targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function mutations caused by imprecise excision of TE insertions have been generated for Dmel\AkhR. Physical and genetic interactions have been described for both genes; see below and in the respective gene reports.
In flies, in addition to the adipokinetic hormone signaling pathway, the PNPLA/ATGL-related pathway regulates storage-fat accumulation and mobilization (see FBhh0000504). Phenotypes are additive: simultaneous loss of a fly PNPLA/ATGL family ortholog (bmm) and the adipokinetic receptor (AkhR) causes extreme obesity and blocks acute storage fat mobilization, even when food-deprived.
[updated Feb. 2019 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).
In mammals, glucagon increases glycemia by promoting catabolism of fat and glycogen. In the fly, adipokinetic hormone (AKH) regulates catabolism of lipids analogously to mammalian glucagon, but AKH does not induce catabolism of glycogen (Galikova and Klepsatel, 2018, and references cited therein; pubmed:29954158; FBrf0239311).
In flies, chronic high-sugar diet, but not acute high-sugar feeding, increases AKH action and elevates glycemic levels. This appears to indicate a pathogenic, but not physiological, enhancement of AKH response in the fat body under chronic high-sugar diet (Song et al., 2017; pubmed:28178568; FBrf0234747).
Dmel\Akh is postulated to play a role analogous to some of the functions of mammalian glucagon.
Moderate-scoring ortholog of human gonadotropin releasing hormone receptor (GNRHR); multiple lower-scoring orthologs in both species. Dmel\AkhR shares 32% identity and 56% similarity with the human GNRHR gene. Dmel\AkhR is less closely related to the human glucagon receptor (GCGR), sharing 25% identity and 41% similarity.
