Brown Adipose Tissue: More Than an Effector of Thermogenesis?a

Brown adipose tissue (BAT) produces heat by oxidation of fatty acids. This takes place when the tissue is stimulated by norepinephrine; the molecular background for the ability of BAT to produce heat is the tissue-specific mitochondrial protein UCP1. In the classic view of BAT with respect to fever, BAT is an effector organ, producing heat especially during the onset phase of the fever. There is good evidence that BAT thermogenesis is stimulated via a lipopolysaccharide (LPS), interleukin (IL)-1 beta, IL-6, prostaglandin E cascade. Under physiologic conditions of constantly stimulated activity, BAT is expected to be recruited, but in fevers this is only evident in thyroxine fever. However, BAT may be more than merely an effector. There are indications of a correlation between the amount of BAT and the intensity of fevers, and brown adipocytes can indeed produce IL-1 alpha and IL-6. Furthermore, brown adipocytes are directly sensitive to LPS; this LPS sensitivity is augmented in brown adipocytes from IL-1 beta-deficient mice. Thus, BAT may also have a controlling role in thermoregulation. The existence of transgenic mice with ablations of proteins central in fever and in BAT thermogenesis opens up possibilities for identification and elucidation of this putative new role for brown adipose tissue as an endocrine organ involved in the control of fever.