Adipose tissue has been ignored by anatomists and physicians for centuries, considered to be an energy storage depot with few interesting attributes. The well-documented rise in obesity during the past 30 years1
has contributed to the negative image of adipose tissue, particularly in the popular mind. The past two decades, however, have seen a wave of intense scientific interest in this cell type, fuelled in part by concerns about obesity and its attendant metabolic sequelae2
, and also by the recognition that adipocytes integrate a wide array of homeostatic processes. In addition to regulating fat mass and nutrient homeostasis (discussed below), adipocytes are involved in the immune response, blood pressure control, haemostasis, bone mass, and thyroid and reproductive function3
. These processes are coordinated mainly through the synthesis and release of peptide hormones by adipocytes.
Adipocytes also release fatty acids into the circulation, which are used by most organs for fuel when glucose is limiting. These fatty acids are generated by breaking down triacylglycerols, which contain more energy per unit mass than do carbohydrates and can essentially be stored anhydrously. By contrast, glycogen has only the half the energy content per unit of pure mass, and must be stored in association with water, further decreasing its efficiency.
Although most multicellular organisms have cells that store excess energy, adipocytes evolved to meet this need at the time of the vertebrate radiation. Mammals, birds, reptiles, amphibians and many (but not all) fish have cells that are readily identifiable as adipocytes, although the anatomical location of fat tissues varies considerably between species4
. Most mammals have stereotypical adipose depots located throughout the body. Some of these depots are thought to be largely structural, providing mechanical support but contributing relatively little to energy homeostasis. Examples include the fat pads of the heels, fingers and toes, and the periorbital fat supporting the eyes. Other adipocytes exist in loose association with the skin, and have been termed subcutaneous fat. These cells are the cause of ‘cellulite’, and are the target of cosmetic procedures such as liposuction. Finally, there are several distinct depots within the body cavity, surrounding the heart and other organs, associated with the intestinal mesentery, and in the retroperitoneum. Some of these depots, known as visceral fat, drain directly into the portal circulation and have been linked to many of the morbidities associated with obesity, including type 2 diabetes and cardiovascular disease. Adipocytes and precursor cells from different depots have different replicative potential, different developmental attributes and different responses to hormonal signals, although the mechanistic basis for these distinctions is still unclear5
In addition to depot-specific differences, a further distinction must be made between brown and white adipocytes. Brown adipocytes are found only in mammals, and differ from the more typical white adipocytes in that they express uncoupling protein-1 (UCP-1), which dissipates the proton gradient across the inner mitochondrial membrane that is produced by the action of the electron transport chain. This generates heat at the expense of ATP. Morphologically, brown adipocytes are multilocular and contain less overall lipid than their white counterparts, and are particularly rich in mitochondria. Rodents have a distinct brown fat pad, which lies in the interscapular region. In humans, brown adipose tissue surrounds the heart and great vessels in infancy but tends to disappear over time until only scattered cells can be found within white fat pads.
This review briefly examines the transcriptional basis of adipocyte development, and then discusses energy homeostasis in mammals and how adipocytes regulate components of that system. The second part of the review provides a similar look at the role of adipose tissue in glucose homeostasis. Adipocytes have a crucial role in regulating both of these physiological processes through a series of endocrine and non-endocrine mechanisms. These involve a widening array of adipose-derived secreted molecules (known as adipokines), neural connections and changes in whole-body physiology wrought by primary alterations in adipocyte cellular metabolism.