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Review
. 2022 Jul 17;11(7):1063.
doi: 10.3390/biology11071063.

Is Brain-Derived Neurotrophic Factor a Metabolic Hormone in Peripheral Tissues?

Elsie Chit Yu Iu  1 , Chi Bun Chan  1
Affiliations
Review

Is Brain-Derived Neurotrophic Factor a Metabolic Hormone in Peripheral Tissues?

Elsie Chit Yu Iu et al. Biology (Basel). .

Abstract

Brain-derived neurotrophic factor (BDNF) is an important growth factor in the central nervous system. In addition to its well-known activities in promoting neuronal survival, neuron differentiation, and synaptic plasticity, neuronal BDNF also regulates energy homeostasis by modulating the hypothalamus's hormonal signals. In the past decades, several peripheral tissues, including liver, skeletal muscle, and white adipose tissue, were demonstrated as the active sources of BDNF synthesis in response to different metabolic challenges. Nevertheless, the functions of BDNF in these tissues remain obscure. With the use of tissue-specific Bdnf knockout animals and the availability of non-peptidyl BDNF mimetic, increasing evidence has reported that peripheral tissues-derived BDNF might play a significant role in maintaining systemic metabolism, possibly through the regulation of mitochondrial dynamics in the various tissues. This article reviews the autocrine/paracrine/endocrine functions of BDNF in non-neuronal tissues and discusses the unresolved questions about BDNF's function.

Keywords: BDNF; metabolism; mitochondria; peripheral tissues.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Synthesis of pro-BDNF and mature BDNF (mBDNF). BDNF mRNA is translated in the endoplasmic reticulum to form pre-pro-BDNF, which is subsequently cleaved to form pro-BDNF. After being transported into the Golgi apparatus, the pro-BDNF is further converted into mBDNF by furin-like protein convertases. Alternatively, pro-BDNF is exported as a functional hormone or is further processed by the tissue type plasminogen activator (tPA) or matrix metalloproteinase (MMP) to form mBDNF extracellularly.
Figure 2
Figure 2
Functional activities of mBDNF in the liver.
Figure 3
Figure 3
Functional activities of mBDNF and pro-BDNF in the white adipose tissue. The mBDNF and pro-BDNF are mainly synthesized by the progenitor cells and macrophages, which act on the mature adipocyte to modulate its metabolism. The BDNFs might also act as an autocrine to modulate the differentiation of pre-adipocytes and the transformation of macrophages.
Figure 4
Figure 4
Functional activities of BDNF in skeletal muscle (Skm). In Skm, mBDNF is produced by the myofiber, satellite cells, and blood vessel endothelial cells. It acts in an autocrine and paracrine manner to modulate the mitochondrial dynamics and lipid metabolism in myofibers, control the myogenesis, and maintain the functions of the neuromuscular junction. The myofiber-generated BDNF is also secreted into circulation to regulate the functions of the pancreas.
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