Globular adiponectin acts as a melanogenic signal in human epidermal melanocytes

Summary

Background

Adiponectin is an adipocyte-derived cytokine which circulates as a full-length protein and a fragment containing the globular domain of adiponectin (gAd). A recent study has reported the anti-melanogenic effects of full-length adiponectin.

Objectives

To examine the involvement of gAd in melanogenesis and its action mechanisms.

Methods

The effects of gAd on melanogenesis and its mechanism of action were investigated in human epidermal melanocytes and reconstructed epidermis, and they included the levels of melanin content, cellular tyrosinase activity, cAMP production and protein kinase A (PKA) activity, expression and phosphorylation of signaling molecules.

Results

Exogenous gAd increased the melanin content, and the mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase and tyrosinase-related protein (TRP)-1, but not TRP-2, were increased by gAd. However, cAMP production and PKA activity were not affected by gAd. Moreover, attempts to elucidate the underlying mechanism behind the gAd-mediated effect revealed that gAd could regulate melanogenesis by upregulating MITF through phosphorylation of the cAMP response element-binding protein (CREB). In addition, upregulation of MITF was mediated through activation of adenosine monophosphate-activated protein kinase (AMPK)-p38MAPK signaling. Taken together, these findings indicate that promotion of melanogenesis by gAd occurs through increased expression of the MITF gene, which is mediated by activation of the AMPK-p38MAPK-CREB pathway.

Conclusions

These findings suggest that gAd contributes to epidermal homeostasis via its effect on melanocyte biology, and products of adipose tissue could affect epidermal biology.

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