Fat for life: new stories on old grease.

DUE TO THE ALARMING EPIDEMIC in the modern world of obesity, dyslipidemia, and the parallel increasing prevalence of the related metabolic and cardiovascular diseases such as type 2 diabetes and atherosclerosis, the neutral lipids triglycerides and cholesteryl esters have a notorious reputation. The excessive accumulation of triglycerides reflects energy surplus, which ultimately causes the excessive adiposity that leads to obesity; in addition, the deposition of cholesteryl esters in the artery walls is an inevitable step for the fatty plaque formation hastening the development of atherosclerosis. Prevention and treatment of neutral lipid-related metabolic and cardiovascular diseases are major challenges for modern medicine. For many years, neutral lipids had been misperceived as “boring grease”. The primary reason is that these lipids are extremely hydrophobic. As a result, the biochemical studies regarding the synthesis and degradation of neutral lipids as well as the elucidation of their metabolic function were largely at the descriptive level. Enzymes involved in the metabolic flux of these lipids are often either intrinsic membrane proteins or favor an extremely hydrophobic environment, which has historically been difficult to isolate through traditional protein purification techniques. Fortunately, in the last two decades, powered with the revolution and the elegant combined use of methodologies in biochemistry, molecular biology, bioinformatics, cell biology, and forward and reverse genetics, we have witnessed an impressive transformation of the neutral lipid field. Today, many steps, if not all, of the neutral lipid metabolic pathways have been revealed in molecular detail. In addition, along with the improved analytic tools, the previously underappreciated complexity of neutral lipids has also started to be revealed. Cases have been identified that establish the relationship between specific species of neutral lipids and specific disease states. The purpose of this review series is to highlight such progress. Because of the richness of the science and the expansion of the field, nine excellent reviews have been divided into four separate parts, each of which will be published in this Journal over the next four consecutive issues.