Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle. Lipotoxicity is believed to have a role in heart failure, obesity, and diabetes, and is estimated to affect approximately 25% of the adult American population. Cause In normal cellular operations, there is a balance between the production of lipids, and their oxidation or transport. In lipotoxic cells, there is an imbalance between the amount of lipids produced and the amount used. Upon entrance of the cell, fatty acids can be converted to different types of lipids for storage. Triacylglycerol consists of three fatty acids bound to a glycerol molecule and is considered the most neutral and harmless type of intracellular lipid storage. Alternatively, fatty acids can be converted to lipid intermediates like diacylglycerol, ceramides and fatty acyl-CoAs. These lipid intermediates can impair cellular function, which is referred to as lipotoxicity. Adipocytes, the cells that normally function as lipid store of the body, are well equipped to handle the excess lipids. Yet, too great of an excess will overburden these cells and cause a spillover into non-adipose cells, which do not have the necessary storage space. When the storage capacity of non-adipose cells is exceeded, cellular dysfunction and/or death result. The mechanism by which lipotoxicity causes death and dysfunction is not well understood. The cause of apoptosis and extent of cellular dysfunction is related to the type of cell affected, as well as the type and quantity of excess lipids. A theory has been put forward by Cambridge researchers relating the development of lipotoxicity to the perturbation of membrane glycerophospholipid/sphingolipid homeostasis and their associated signalling events. Currently, there is no universally accepted theory for why certain individuals are afflicted with lipotoxicity. Research is ongoing into a genetic cause, but no individual gene has been named as the causative agent. The causative role of obesity in lipotoxicity is controversial. Some researchers claim that obesity has protective effects against lipotoxicity as it results in extra adipose tissue in which excess lipids can be stored. Others claim obesity is a risk factor for lipotoxicity. Both sides accept that high fat diets put patients at increased risk for lipotoxic cells. Individuals with high numbers of lipotoxic cells usually experience both leptin and insulin resistance. However, no causative mechanism has been found