The membrane receptor CD44: novel insights into metabolism

CD44, a cell-surface glycoprotein, has long been studied as a cancer molecule due to its essential role in physiological activities in normal cells and pathological activities in cancer cells, such as cell proliferation, adhesion, and migration; angiogenesis; inflammation; and cytoskeleton rearrangement. Yet, recent evidence suggests a role of CD44 in metabolism, especially insulin resistance in obesity and diabetes. In line with the current concept of fibroinflammation in obesity and insulin resistance, CD44 as the main receptor of the extracellular matrix component, hyaluronan (HA), has been shown to regulate diet-induced insulin resistance in muscle and other insulin-sensitive tissues. In this review, we integrate current evidence for a role of CD44 in regulating glucose and lipid homeostasis and speculate about its involvement in the pathogenesis of chronic metabolic diseases, including obesity and diabetes. We summarize the current development of CD44-targeted therapies and discuss its potential for the use in treating metabolic diseases.