Sunji LeeHong BaoZachary IshikawaWeidong WangHui-Ying Lim2017-04-102017-04-102017-01-17Lee S, Bao H, Ishikawa Z, Wang W, Lim H-Y (2017) Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila. PLoS Genet 13(1): e1006555. doi:10.1371/journal.pgen.1006555http://hdl.handle.net/11244/50423We thank our colleagues Linda Thompson and Luke Szweda at OMRF, and Gary Struhl at Columbia University for critical comments on the manuscript. We are grateful to Rolf Bodmer (Sanford-Burnham-Presby Medical Discovery Institute), Joquim Culi (CSIC-UPO), Susan Abmayr (Stowers Institute) and Laurent Perrin (TAGC) for fly stocks and antibodies. We also thank the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi Center, and the TRiP at Harvard Medical School for fly stocks. We acknowledged the Imaging Core Facility at OMRF for excellent technical assistance.Author Summary The heart is increasingly recognized to serve an important role in the regulation of whole-body lipid homeostasis; however, the underlying mechanisms remained poorly understood. Here, our study in Drosophila reveals that cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body (insect liver and adipose tissue). We found that apoB-lipoproteins generated by the Drosophila cardiomyocytes serve an equally significant role as their fat body-derived counterparts in maintaining systemic lipid homeostasis on normal food diet. Importantly, on high fat diet (HFD), the cardiomyocyte-derived apoB-lipoproteins are the major determinants of whole-body lipid metabolism, a role which could be attributed to the HFD-induced up-regulation of apoB-lipoprotein biosynthesis genes in the cardiomyocytes and their down-regulation in the fat body. Taken together, our results reveal that apoB-lipoproteins are new players in mediating the heart control of lipid metabolism, and provide first evidence supporting the notion that HFD-induced differential regulation of apoB-lipoprotein biosynthesis genes could alter the input of different tissue-derived apoB-lipoproteins in systemic lipid metabolic control.en-USAttribution 3.0 United StatesFats,Larvae,Lipid metabolism,Heart,Gastrointestinal tract,Lipids,Diet,Drosophila melanogasterResearch Article10.1371/journal.pgen.1006555false