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Chapter 19 Regulation of proliferation, differentiation and apoptosis of brown adipocytes: Signal transduction pathways involved

DOI: 10.1016/s1568-1254(02)80021-3
  • Biology


Publisher Summary Brown adipose tissue (BAT) is characterized by the presence of the uncoupling protein- 1 (UCP- 1) in the mitochondrial inner membrane, which allows the production of heat by the mechanism called “non-shivering thermogenesis.” BAT development, function, and involution are controlled by many extracellular signals, which regulate proliferation, differentiation and apoptosis of brown adipocytes. Some, such as T3 or retinoic acid, bind to their nuclear receptors—trans-activating ucp-1 gene—while others bind to membrane receptors activating different signaling pathways. Among these pathways, ERKs, PI3K, p38MAPK, and the cAMP/PKA cascades are of particular relevance. Activation of ERKs is required for proliferation and survival induced by several signals, while playing a negative role in differentiation. In contrast, PI3K mediates IGF-I/insulin-induced differentiation and cAMP/PKA cascade is essential for NA-induced UCP-1 expression. On the other hand, p38MAPK is currently identified as an important mediator of differentiation and apoptosis upon activation by different extracellular signals.

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