[HTML][HTML] Inhibition of serotonin synthesis induces negative hepatic lipid balance
Diabetes & metabolism journal, 2018•ncbi.nlm.nih.gov
Background Hepatic steatosis is caused by metabolic stress associated with a positive lipid
balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity
effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and
hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid
accumulation. Here, we showed the possibility of direct action of serotonin on hepatic
steatosis. Methods Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 …
balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity
effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and
hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid
accumulation. Here, we showed the possibility of direct action of serotonin on hepatic
steatosis. Methods Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 …
Abstract
Background
Hepatic steatosis is caused by metabolic stress associated with a positive lipid balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we showed the possibility of direct action of serotonin on hepatic steatosis.
Methods
Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate diet (HCD) to induce hepatic steatosis. Hepatic triglyceride content and gene expression profiles were analyzed.
Results
Pharmacological and genetic inhibition of serotonin synthesis reduced HFD-induced hepatic lipid accumulation. Furthermore, short-term PCPA treatment prevented HCD-induced hepatic steatosis without affecting glucose tolerance and browning of subcutaneous adipose tissue. Gene expression analysis revealed that the expressions of genes involved in de novo lipogenesis and triacylglycerol synthesis were downregulated by short-term PCPA treatment as well as long-term PCPA treatment.
Conclusion
Short-term inhibition of serotonin synthesis prevented hepatic lipid accumulation without affecting systemic insulin sensitivity and energy expenditure, suggesting the direct steatogenic effect of serotonin in liver.
ncbi.nlm.nih.gov