Abstract
Currently about 2 billion adults globally are estimated to be overweight and ~13% of them are obese. High fat diet (HFD) is one of the major contributing factor to obesity, heart disease, diabetes and cancer. Recent findings on the role of HFD in inducing abnormalities in neurocognition and susceptibility to Alzheimer’s disease are highly intriguing. Since fundamental molecular pathways are often conserved across species, studies involving Drosophila melanogaster as a model organism can provide insight into the molecular mechanisms involving human disease. In order to study some of such mechanisms in the central nervous system as well in the rest of the body, we investigated the effect of HFD on the transcriptome in the heads and bodies of male and female flies kept on either HFD or regular diet (RD). Using comprehensive genomic analyses which include high-throughput transcriptome sequencing, pathway enrichment and gene network analyses, we found that HFD induces a number of responses that are sexually dimorphic in nature. There was a robust transcriptional response consisting of a downregulation of stress-related genes in the heads and glycoside hydrolase activity genes in the bodies of males. In the females, the HFD led to an increased transcriptional change in lipid metabolism. A strong correlation also existed between the takeout gene and hyperphagic behavior in both males and females. We conclude that a) HFD induces a differential transcriptional response between males and females, in heads and bodies and b) the non-dimorphic transcriptional response that we identified was associated with hyperphagia. Therefore, our data on the transcriptional responses in flies to HFD provides potentially relevant information to human conditions including obesity.
Highlights
Diet consisting of high saturated fat (HFD) is a risk factor associated with cardiovascular disease (CVD) [1,2,3]
We found that female w1118 flies kept on high-fat diet (HFD) showed a significant increase in whole-body TG levels when compared to flies kept on regular diet (RD) (P
In the bodies, more genes were downregulated in the males and opposite in the females (Fig 2G and 2H). These results indicate that male flies when kept in HFD are more responsive or sensitive to the HFD
Summary
We used Jazz Mix Drosophila food from New Horizon Foods. For the regular diet (RD), as directed by New Horizon Foods, we added 800mL of distilled water to 151g food mix and heated to boil the mixture and placed 1mL each in regular size plastic vials. For the high-fat diet (HFD), as adopted in Heinrichsen et al, 2012, we added 20% weight per volume of foodgrade coconut oil (Aunt Patty’s Organic Coconut Oil) to the regular food [32, 34]. The hot food was stirred well until the oil is dissolved. Similar to the RD 1mL of medium was dispensed into each vial occasionally stirring the stock container
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