Similar to the mammalian hepatocytes, Drosophila oenocytes accumulate fat during fasting, but it is unclear how they communicate with the fat body, the major lipid source. Using a modified protocol for prolonged starvation, we show that knockdown (KD) of the sole delta 9 desaturase, Desat1 (SCD in mammals), specifically in oenocytes leads to more saturated lipids in the hemolymph and reduced triacylglycerol (TAG) storage in the fat body. Additionally, oenocytes with Desat1 KD exhibited an accumulation of lipoproteins and actin filaments at the cortex, which decreased lipoproteins in the hemolymph. We further show that ImpL2 (IGFBP7 in mammals) is secreted from oenocytes during starvation in a Desat1-dependent manner. Flies with oenocyte-specific KD and overexpression of ImpL2 exhibited higher and lower sensitivity to starvation as well as lower and higher levels of TAG, respectively. Intriguingly, the depolymerization of cortical actin in the oenocytes decreased lipoprotein sequestration and alleviated the secretion defect of Impl2 in Desat1 KD cells, leading to rescued TAG levels and starvation sensitivity. Overall, this study highlights the central role of oenocytes in systemic lipid metabolism in Drosophila as well as the importance of Desat1 in maintaining the proper functioning of oenocytes during periods of starvation.