This report describes a model of obesity and cardiomyocyte regulation of systemic lipid levels using the Drosophila gene apolpp. Dmel\apolpp is orthologous to the human gene APOB, which encodes a major protein constituent of low density lipoproteins; it also functions as a recognition signal for the cellular binding and internalization of LDL particles. APOB is implicated in two diseases caused by aberrant levels of apolipoprotein B-containing lipoproteins (see MIM:107730). RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\apolpp.
Constructs carrying the matrix attachment region (MAR) of the human Hsap\APOB gene have been introduced into flies. The gene has not been characterized in flies in the context of this disease model.
The role of Dmel\apolpp in the regulation of systemic lipid levels was investigated due to the fact that Dmel\Mtp is known to be an essential factor in the assembly and secretion of the major apoB-lipoproteins (see the human disease model report 'obesity and cardiomyocyte regulation of systemic lipid levels, MTTP-related' (FBhh0001197). Similar to phenotypes observed for Dmel\Mtp knockdown, knockdown of apolpp specifically in the fat body results in a significant reduction in whole-body triglyceride levels on a normal fat-diet (NFD), however, it does not ameliorate the increase in triglyceride levels precipitated by a high-fat diet (HFD). Knockdown of apolpp specifically in cardiomyocytes results in a significant reduction in whole-body triglyceride levels on a NFD and a highly significant decrease in whole-body triglyceride levels on a HFD, relative to that observed for control animals.
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, SNAIL TF genes-related' (FBhh0001199);'obesity, susceptibility to (postulated), MED13-related' (FBhh0000506); 'obesity, susceptibility to (postulated), MED12-related' (FBhh0000507).
Dmel\apolpp appears to play a role in the process of body-fat assessment. The prothoracic gland (PG) of insects plays a key role in sexual maturation; an initial step in this process is body-fat assessment. Using RNAi targeted to the larval prothoracic gland, larvae with knockdown of apolpp in the PG fail to initiate maturation despite accruing sufficient fat stores. See also 'obesity, body-fat sensor mechanisms, semaphorin-related' (FBhh0001409).
[updated Nov. 2021 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)
Autosomal dominant familial hypercholesterolemia-2 (FCHL2) is caused by heterozygous mutation in the APOB gene. [from MIM:144010; MIM:107730; 2020.02.24]
Familial hypobetalipoproteinemia-1 (FHBL1), an autosomal recessive disorder, is caused by mutation in the APOB gene. [from MIM:615558; 2020.02.24]
Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48) and low density lipoproteins (apo B-100). Apo B-100 functions as a recognition signal for the cellular binding and internalization of LDL particles by the apoB/E receptor. [Gene Cards, APOB; 2020.02.24]
One to many (1 human to 2 Drosophila).
