Adipose tissue expands to accommodate increased lipid through hypertrophy of existing adipocytes and by initiating differentiation of preadipocytes. The capacity of adipose tissue to expand is critical for accommodating changes in energy availability, but this capacity is not an unlimited process and likely varies between individuals. We suggest that it is not the absolute amount of adipose tissue but rather the capacity of adipose tissue to expand that affects metabolic homeostasis. Here we highlight examples of disease states and transgenic animal models with altered adipose tissue function that support this hypothesis and discuss possible mechanisms by which altered adipose tissue expandability impairs metabolic homeostasis

Clinical observations and experiments using genetically modified mouse models, some of which are discussed here, demonstrate that our understanding of how adipose tissue affects metabolic homeostasis is still developing. Although we know that obesity is a major health concern that predisposes individuals to many secondary conditions, including insulin resistance and type 2 diabetes, we suggest that it is not the absolute amount of adipose tissue that determines the metabolic disruption, but rather limited expansion capacity of the adipose tissue (Figure 1). Identifying adipose tissue expandability as an important factor in preventing lipotox-icity and associated metabolic complications may introduce new therapeutic approaches that promote adipose tissue storage capacity. Although this is a counterintuitive suggestion for the treatment of obesity-related diabetes, this would expand the safe storage depot for lipid and prevent the accumulation of toxic lipid species in non-adipose tissues.