METRNL

Official Full Name

meteorin like, glial cell differentiation regulator

Organism

Homo sapiens

GeneID

284207

Background

Predicted to enable hormone activity. Predicted to be involved in several processes, including brown fat cell differentiation; positive regulation of brown fat cell differentiation; and response to muscle activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Feb 2025]

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Detailed Information

Metrnl and the neurotrophic regulator Meteorin form a secreted protein family. The Metrnl precursor protein fragment of human, rat and mouse is approximately 31 kDa. Studies have shown that Metrnl has low levels of expression in brain tissue, including the forebrain, midbrain, and hindbrain of brain and adult mice during mouse development. Other studies have shown that Metrnl is expressed in various tissues of the body, including heart, liver, spleen, lung, kidney, fat, digestive tract, muscle, blood, pancreas, etc., but the expression level is different. Metrnl is highly expressed in subcutaneous white fat, stomach intestines and skin.

The Role of Metrnl

Studies have shown that Metrnl, like its homologous protein Meteorin, also has neurotrophic nutrition, which promotes the elongation of the nerves of the dorsal roots and the migration of the nerves. It also has the protective effect of the ear. In addition, studies at the RNA level have also shown that Metrnl is involved in the synaptic elongation of the nerves and supports its cultivating role.

Studies have shown that Metrnl plays an important role in the regulation of the formation and biological function of white adipose tissue. In particular, fat Metrnl can counteract insulin resistance induced by high-fat diet or caused by leptin gene deficiency, suggesting that Metrnl is expected to be a new target for the treatment of obesity and related metabolic diseases. The study proves that Metrnl plays an important role in the process of white fat browning during cold and cold stimulation. In addition, Metrnl expressed higher levels in fat cells of obese children than in normal groups.

Figure 1. Known functions of Metrnl in white adipose tissue and neurocytes. (Zheng, S. L., et al. 2016)

Metrnl Regulates Beige Fat

Human adipose tissue is generally divided into white adipose tissue (WAT) and brown adipose tissue (BAT). There is also an inducible brown fat in WAT, which is named "beige fat". Metrnl is a new cytokine that regulates the formation of beige fat. The study found that Metrnl promotes IL-4/IL-13 synthesis by activating eosinophils. The study found that low temperature can induce the synthesis of IL4/IL-13 molecules, and activates M2 macrophages via signal transduction and transcriptional activator 6 (STAT6) signaling, thereby making the expression of marker gene of M2 macrophage - Argl, Mrcl Clec10a significantly up-regulated. Meanwhile, the synthesis of inflammatory response factors was inhibited, and catecholamines were released to act on WAT, thereby regulating heat production and fatty acid metabolism.

The expression of Metrnl in mice was increased by intravenous injection of the expression vector of Metrnl. The study found that the level of Metrnl in the serum increased 3 days after the injection, and the activated eosinophils increased, and peaked on the fourth day. The results showed that Metrnl first stimulated the secretion of IL4/IL-13 by eosinophils, which promoted the expression of the thermogenic gene UCP1, thereby regulating the formation of beige fat and regulating energy metabolism. Other studies have shown that the IL-4/IL-13-STAT6 immune pathway is impaired, and the production of beige adipose tissue is reduced, and the energy consumption is reduced. Therefore, it is implied that the L-4/IL-13-STAT6 signal transduction pathway plays an important role in regulating beige lipogenesis.

References:

Li, Z. Y. , Song, J. , Zheng, S. L. , Fan, M. B. , Guan, Y. F. , & Qu, Y. , et al. (2015). Adipocyte metrnl antagonizes insulin resistance through pparγ signaling. Diabetes, db150274.
Löffler D., Landgraf, K., Rockstroh, D. , Schwartze, J. T. , Dunzendorfer, H. , & Kiess, W. , et al. (2016). Meteorin-like (metrnl) decreases during adipogenesis and inhibits adipocyte differentiation leading to adipocyte hypertrophy in humans. International Journal of Obesity.
Zheng, S. L., Li, Z. Y., Song, J., Liu, J. M., & Miao, C. Y. (2016). Metrnl: a secreted protein with new emerging functions. Acta Pharmacol Sin, 37(5), 571-579.

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