Non-sympathetic control of brown adipose tissue.

The thermogenic activity of brown adipose tissue (BAT) in the organism is tightly regulated through different processes, from short-term induction of uncoupling protein-1-mediated mitochondrial proton conductance to complex processes of BAT recruitment, and appearance of the beige/brite adipocytes in white adipose tissue (WAT), the so-called browning process. The sympathetic nervous system is classically recognized as the main mediator of BAT activation. However, novel factors capable of activating BAT through non-sympathetic mechanisms have been recently identified. Among them are members of the bone morphogenetic protein family, with likely autocrine actions, and activators of nuclear hormone receptors, especially vitamin A derivatives. Multiple endocrine factors released by peripheral tissues that act on BAT have also been identified. Some are natriuretic peptides of cardiac origin, whereas others include irisin, originating in skeletal muscle, and fibroblast growth factor-21, mainly produced in the liver. These factors have cell-autonomous effects in brown adipocytes, but indirect effects in vivo that modulate sympathetic activity toward BAT cannot be excluded. Moreover, these factors can affect to different extents such as the activation of existing BAT, the induction of browning in WAT or both. The identification of non-sympathetic controllers of BAT activity is of special biomedical interest as a prerequisite for developing pharmacological tools that influence BAT activity without the side effects of sympathomimetics.