Non-sympathetic control of brown adipose tissue

Abstract

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.

Factors involved in white‐to‐brown adipose tissue conversion and in thermogenesis: a review

“…The fibroblast growth factor 21 (FGF21) is an endocrine factor involved in the regulation of hepatic lipid metabolism, glycaemia and the functionality of pancreatic β‐cells, and it is mainly produced by liver . In adipose cells FGF21 interacts with the FGF receptor and its co‐receptor β‐Klotho.…”

Activin E Controls Energy Homeostasis in Both Brown and White Adipose Tissues as a Hepatokine

“…Although activation of brown and beige adipocytes may be a promising strategy against obesity, pharmacological activation of the sympathetic nervous system is not considered as a potential therapy because of strong side effects on the cardiovascular system (Yen and Ewald, 2012). Thus, identification of non-sympathetic regulators of brown and beige adipocyte activity has attracted great interest (Cereijo et al, 2015). Several factors, such as Fgf21, Bmp8b, and Irisin, have been shown to regulate brown and beige adipogenesis and activation of brown and beige adipocytes (Harms and Seale 2013).…”

Increased FGF21 in brown adipose tissue of tyrosine hydroxylase heterozygous mice: implications for cold adaptation

“…This batokine has been previously found to be increased under various situations including starvation, ketogenic diets, and overfeeding, as well as by deficiency or excess in dietary proteins and carbohydrates, respectively (43,55). Although FGF21 is mainly synthetized and released by the liver (56), the BAT is another source of FGF21, where it has autocrine/paracrine functions related to upregulation of UCP-1 and thermogenesis (19,57). We also found elevated FGF21 in the plasma from Th +/ mice, an effect that could be explained by the increased liver expression and secretion.…”