De novo lipogenesis (DNL) is a complex and highly regulated process in which carbohydrates from circulation are converted into fatty acids that are then used for synthesizing either triglycerides or other lipid molecules. Dysregulation of DNL contributes to human diseases such as obesity, type 2 diabetes, and cardiovascular diseases. Thus, the lipogenic pathway may provide a new therapeutic opportunity for combating various pathological conditions that are associated with dysregulated lipid metabolism. Hepatic DNL has been well documented, but lipogenesis in adipocytes and its contribution to energy homeostasis and insulin sensitivity are less studied. Recent reports have gained significant insights into the signaling pathways that regulate lipogenic transcription factors and the role of DNL in adipose tissues. In this review, we will update the current knowledge of DNL in white and brown adipose tissues with the focus on transcriptional, post-translational, and central regulation of DNL. We will also summarize the recent findings of adipocyte DNL as a source of some signaling molecules that critically regulate energy metabolism.