George N Chaldakov Anton B Tonchev Nese Tuncel Pepa Atanassova and Luigi Aloe

Chemo Secrets From a Breast Cancer Survivor

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Abstract

Recently, the endocrine activity of adipose tissue cells has been intensively studied. In effect, a wide range of exported secretory proteins, dubbed adipokines, have been identified as constituents of the adipose proteome (adipokinome). Besides their effects on glucose and energy metabolism, adipokines are potent modulators of inflammation. This chapter provides a state-of-the-science review of adipokine-mediated paracrine signaling that may be implicated in the pathogenesis of inflammation-related diseases such as atherosclerosis, thyroid-associated ophthalmopathy, and breast cancer. We also point out a possible contribution of adipose tissue-associated mast cell secretory activity to the development of these diseases. Finally, we provide arguments for yin-yang (protective vs pathogenic) roles of adipokines in inflammation. This hypothesis may provide further novel drug targets for the development of adipopharmacology of inflammatory diseases.

Key Words: Adipobiology; atherosclerosis; breast cancer; epicardial adipose tissue; ophthal-

Today, increasing attention is being focused on the importance of adipose tissue in disease (1), one of the most exciting examples being the rapidly growing interest in understanding the adipose tissue secretion of signaling proteins collectively designated adipokines (2-5). These multifunctional molecules, via endocrine and paracrine pathways (6,7), are potent modulators of inflammation (reviewed in refs. 5,8-11).

This chapter reviews data of adipose tissue paracrine signaling in the pathogenesis of low-grade inflammation-related diseases such as atherosclerosis, thyroid-associated ophthalmopathy, and breast cancer. We also point out a possible contribution of adipose mast cell secretory activity to the development of these disorders. Finally, we provide arguments for differential, yin-yang (protective vs pathogenic) roles of adipokines in inflammation-related diseases. This may provide basis of adipose tissue-targeted pharmacology.

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