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Very low-density lipoproteins (VLDL), along with chylomicrons, low-density lipoproteins (LDL), intermediate-density lipoproteins (IDL), and high-density lipoproteins (HDL) are the 5 major types of lipoproteins. These lipoproteins transport hydrophobic lipids such as phospholipids, triglycerides, and cholesterol in the plasma and extracellular fluids. Lipids, proteins, carbohydrates, and nucleic acids are the main components of cellular life. Lipids are vital for synthesizing cell membranes, energy storage, intracellular messaging, and transporting other essential organic substances such as vitamins. Lipoproteins allow for the transport of hydrophobic lipids in the hydrophilic environment of the body’s systemic circulation.[1] The synthesis and secretion of VLDL into circulation by the liver is a highly complex and regulated process that plays a fundamental role in the overall homeostasis of lipids in the body. Recent evidence has shown that the enhanced production and secretion of VLDL or alterations in its regulatory system directly contribute to developing multiorgan diseases such as atherosclerosis.[2][3][4] There is an ongoing research effort to understand better the basic and complicated mechanisms behind the regulation and signaling of VLDL biogenesis to develop effective targeted therapies in the future.

Diet, sex, and race are factors that significantly influence VLDL production and secretion. VLDL synthesis is mainly related to lipid intake, with secretion increasing in the postprandial state. High-fat diets have been associated with higher VLDL secretion, usually presenting as increased blood triglyceride levels.[21][22] Studies have inconsistently reported the timing of postprandial VLDL peaks, ranging from 30 minutes up to 5 or 6 hours. Nonetheless, multiple studies have found that insulin resistance, metabolic syndrome, and obesity are strongly associated with longer plateaus and higher peaks of VLDL levels.[23][24] Women have also been shown to have lower VLDL concentrations than men, although the cause of this sex difference is not completely understood.[25] VLDL has been associated with the development of multiple pathological conditions involving the cardiovascular, endocrine, renal, hepatic, and nervous systems, as well as cancer and several autoimmune and dermatological diseases.