Serotonin prevents differentiation into brown adipocytes and induces transdifferentiation into white adipocytes.

Background/objectives: Serotonin is synthesized by many cells in the periphery to affect vasoconstriction, intestinal motility, and glucose and lipid metabolism. It has recently been shown that serotonin leads to fat accumulation in white adipose tissue (WAT). However, the direct effect of serotonin on brown adipose tissue differentiation and metabolism is limited. Therefore, our aim was to investigate the effect of serotonin on brown adipocyte metabolism and differentiation.

Methods: Non-differentiated HIB1B cells and differentiated HIB1B brown adipocytes were treated with serotonin and their metabolism and differentiation examined.

Results: Differentiated HIB1B brown adipocytes treated with serotonin had reduced levels of the thermogenic markers uncoupling protein 1 (UCP1) and fibroblast growth factor 21 (FGF21) and increased levels of UCP2. In parallel, serotonin led to 3-6-fold reduction in the gene expression of brown adipocyte differentiation markers, that is, Prdm16 (positive regulatory domain 16), Bmp7 (bone morphogenic protein 7) and Pparγ (peroxisome-proliferator-activated receptor γ). Serotonin treatment reduced catabolism and mitochondrial activity shifting metabolism towards fatty acid synthesis rather than oxidation. Strikingly, non-differentiated HIB1B preadipocytes incubated with serotonin failed to differentiate into brown adipocytes. Moreover, although BMP6-treated myoblasts can readily differentiate into brown adipocytes, serotonin interfered with this process.

Conclusions: Serotonin leads to whitening of brown adipocytes, shifting their metabolism to fat accumulation rather than oxidation. In addition, serotonin interferes with the differentiation process into brown adipocytes.