The Adipocyte as an Endocrine Cell

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Adipose tissue contains many cell types. Among the more abundant are adipocytes, preadipocytes, immune cells, and endothelial cells. During times of excess caloric intake, these cells have to adjust and remodel to accommodate the increased demand for triglyceride storage. Based on a comprehensive analysis of the total adipose tissue secretome, this article focuses on three areas of adipokine biology: (1) How does the adipocyte interact with the extracellular matrix over the course of obestiy? (2) Does the adipocyte, per se, play a role in the innate immune response? (3) How is the angiogenic profile of adipose tissue linked to the development of insulin resistance? The authors present a comprehensive overview of all of the currently available secreted adipose tissue products that have been identified at the protein level.

Section snippets

The adipocyte secretome

So far, much attention in the study of adipocyte-derived factors (so-called “adipokines”) has been devoted to the study of a few proteins with important physiologic functions. Notably, these include leptin, adiponectin, resistin, interleukin 6 (IL-6), monocyte chemotractant protein 1, and tumor necrosis factor alpha (TNF-α). On the other hand, several proteomic approaches in primary and tissue culture–derived 3T3-L1 adipocytes have emphasized the complex nature of the adipocyte secretome,

The extracellular matrix of adipose tissue

During the progression from the lean to the obese state, adipose tissue undergoes hyperplasia and hypertrophy in an attempt to cope with the increased demand for triglyceride storage. Therefore, the extracellular matrix of adipose tissue faces unique challenges with respect to adjusting to the need for remodeling and expansion.

The changes in cell morphology seen during differentiation in cell culture of preadipocytes to adipocytes and the accompanying impact on the expression of various

The immune-regulatory role of the adipocyte

Many adipocyte-derived factors play an intricate role in various aspects of the innate and adaptive immune response (see Table 1). They may be directly involved as chemokines or cytokines, or they may play a regulatory role [28]. It is therefore not surprising that local, obesity-driven changes in adipokine secretion have a systemic impact on several branches of the immune system. The best described phenomenon relates to changes in the inflammatory status. Many aspects of the interactions

Angiogenesis

Although adipocytes occupy the bulk of the volume of adipose tissue, the adipose tissue stroma contains many more cell types that at least equal the adipocytes in number. Nonadipocytic cell types in adipose tissue include fibroblastic preadipocytes that can be triggered to embark on the adipogenic differentiation pathway. Other cell types include immune cells and, importantly, endothelial cells. New endothelium may sprout from existing endothelial cells or it may occur through maturation of new

Posttranslational regulation of adipokine secretion

The authors have described the tremendous versatility of the adipose tissue proteome and have focused their summary mostly on the local effects of adipokines in adipose tissue proper. These effects, of course, also translate into systemic physiologic changes that, in turn, are further modified by adipokines that have endocrine functions and exert their effects on target cells not directly exposed to adipose tissue. A wealth of information is available on the transcriptional regulation of many

The adipocyte secretory pathway

Is this ERp44/Ero1-mediated pathway a widely used mechanism to shunt proteins through later stages of the secretory pathway? Is it also used by other adipokines? At least one other adipokine, resistin, does not get retained in the ER by ERp44 [67], arguing that this mechanism is at least partially specific for adiponectin. However, we still know little about the mechanisms by which the adipocyte handles the differential release of factors to the extracellular environment. Is a triggered release

Summary

The role of adipose tissue as an important source of local mediators in the stroma of a host of organs and its role as an endocrine gland are now widely appreciated. As a whole, adipose tissue can make up a significant proportion of total body weight. So by sheer mass action, it is difficult to ignore the contribution it makes to plasma protein. In addition, because fat pads are interspersed in many different places systemically, they constitute different “miniorgans” with unique

Acknowledgments

The authors would like to thank Nancy Heard for help with the cartoon.

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