Estimated to afflict some 500 million people worldwide, obesity is an increasingly common problem. Numerous studies also implicate it as the number one preventable cause of death globally. Despite these realities, research into the causes and treatments of obesity are handicapped by our limited understandings into the connection between lipid metabolism—the process by which the body breaks down and makes use of lipids—and its related diseases.

Capitalizing on the increased attention to obesity and the need to understand how the underlying genes across animal species control and/or contribute to metabolism, ZHANG Yuru and LIANG Bin of the Kunming Institute of Zoology (KIZ), Chinese Academy of Sciences (CAS), undertook a study aimed at mapping out the genomic and functional conservation of lipid metabolism from the nematode C. elegans to humans by systematically analyzing the genes involved in lipid metabolism in several different species.

By constructing a database of　 471 lipid metabolic genes from the genome of C. elegans, LIANG’s team was able to further assign most of these into different lipid metabolic pathways and then systematically compare these genes to those found in the genomes of humans, Drosophila, mice, and rats. Starting out with nearly 20,000 disease-related genes present in humans, LIANG’s group narrowed this down to 1264 genes related to human metabolic disorders and another 581 related to lipids, 97 of which overlapped as being both related to diseases and lipids. Interestingly, 94 of the 471 lipid metabolic genes in C. elegans are orthologs of human metabolic disease genes and were completely overlapped with the 97 human genes related to similar metabolic problems. 

Using RNA-mediated interference (RNAi) to disrupt the expression of most of these lipid metabolic genes, they were also able to the biological roles these genes play regulating lipid metabolism in simpler organisms like nematodes. Liang’s team found that 21 genes strongly affected fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been connected to the regulation of fat metabolism and related phenotypes. 

This study is a valuable step in understanding the genetic basis of lipid metabolism and certain metabolic disorders that often lead to obesity, such as type 2 diabetes, atherosclerosis,

hypertension, non-alcoholic fatty liver disease, and the like. Moreover, this is the first systematic genomic insight into lipid metabolism in C. elegans and its subsequent connection to related human diseases, greatly enhancing our understanding of the genes involved in both lipid metabolism and its associated disorders across a variety of species. Hopefully these insights will allow us to more efficiently study obesity and begin developing new treatment options, while also contributing to our knowledge of how humans differ from other animal species.

The full text was recently published in BMC Genomics 14:164. Read the full text here: http://www.biomedcentral.com/1471-2164/14/164.

-- Composed by Andrew Willden, Kunming Institute of Zoology