Adipose Cell. History

THE FAT CELL, adipose cell or adipocyte when mature, is approximately 95% triglyceride by weight. The cell consists of a large lipid droplet surrounded by a thin layer of cytoplasm and contained within a cell envelope. The cell is active metabolically and is responsive to nerve and hormonal control as well as to nutritional influences.

The cell converts glucose and triglyceride taken up from the circulating blood and extracellular space to fatty acids and subsequently to stored triglyceride. Stored triglyceride is released by the cell as fatty acids and glycerol—the former used as fuel by working muscle and other tissues. The fine structure of the cell, as revealed by electron microscopy, is complex but reasonably understood in terms of function. Both cell size and number show considerable intraindividual variation.

The stored lipid in the cell contains not only triglyceride but also free cholesterol, some cholesterol esters, and a small pool of free fatty acids. Although white adipose tissue is by far the most dominant form in mature individuals, brown fat exists in the newborn with perhaps some vestages remaining in the adult. Brown fat has distinctly different features than white fat and is thought to play a role in body temperature regulation, particularly in the newborn.

History. In 1857, benign and malignant tumors in adipose tissue were first described with the concept that adipose tissue was made up of connective tissue cells burdened with fat. Although some researchers supported this view, others thought that adipose tissue was unique, and this uniqueness was traced to the embryonic development and further maturation of fat cells in people. Around 1926, studies on the metabolism of adipose tissue were initiated.

The upshot of this early work established the individuality of adipose tissue with respect to its development and metabolism. Perhaps the first suggestion that fat might be synthesized in the adipose tissue itself was provided in 1902 and 1903 based on observations of force-fed geese.

Several investigators have demonstrated the importance of neuroinnervation to the accumulation of stored lipid in adipose tissue. Denervation of adipose tissue, for whatever reason, led to the accumulation of stored lipid. Wertheimer and Shapiro published a classic review in which they emphasized the incorporation of metabolic substrates into stored lipid in adipose tissue and inferred fatty-acid synthesis as an effect of insulin. Subsequently, the important role played by insulin was clarified. Furthermore, glucose incorporation into triglyceride stored in adipose tissue has been demonstrated.

Equally important to the storage of lipid in adipose tissue is the release of substrates from it. Various researchers have independently observed free fatty acids released from adipose tissue with fasting and epinephrine administration. Others found that adipose tissue incubated in vitro also released free fatty acids, a process that was inhibited by glucose and insulin but enhanced by several hormones. In 1962, glycerol release from adipose tissue was demonstrated to track lipolysis, and glycerol and free fatty acids were found to be released together.

In 1964, adipose tissue was shown to be disrupted by collagenase so that single adipocytes were released. These fat cells (adipocytes) could be incubated in an appropriate medium and studied in vitro. Much of what we know about the function of adipocytes is dependent on this technique.

Another important methodological advance was the sizing and counting of adipocytes. Thus, the number of lipid-containing cells could be calculated, which led to the concepts of hypertrophy (large cells) and hyperplasia (large number of cells) of adipocytes. Still, a further technological contribution came from the revival of the connective tissue issue with the discovery that a special cell line (3T3 cells) resembling connective tissue cells could take on the characteristics of adipocytes; these cells have since served as a model system for study of enzymes in the control of adipocyte metabolism.