SEIPIN overexpression in the liver may alleviate hepatic steatosis by influencing the intracellular calcium level
2019
Li, Qiang | Li, Yixing | Zhang, Zhiwang | Kang, Huifang | Zhang, Lifang | Zhang, Yuxiang | Zhou, Lei
SEIPIN deficiency leads to a severe lipodystrophic phenotype with loss of fat tissue. Interestingly, SEIPIN knockout in non-adipocytes is reported to promote intracellular triacylglycerol (TG) accumulation. However, the underlying mechanisms remain unclear at present. Here, we have shown that SEIPIN knockdown and overexpression exert opposite effects on hepatic lipometabolism. Our experimental data suggest that depletion of SEIPIN induces an increase in intracellular TG via activation of ER stress while its overexpression triggers a decrease in the intracellular TG content via increasing PGC-1α, which drives increased mitochondrial activity. Adeno-associated virus-mediated SEIPIN overexpression alleviated high fat diet-induced hepatosteatosis in mice. The collective results indicate that the effects of SEIPIN on TG and PGC-1α are dependent on calcium concentrations, signifying regulatory activity on hepatic lipometabolism through alterations in the intracellular calcium level, and support the potential utility of modulating intracellular SEIPIN and calcium levels as novel therapeutic strategies for fatty liver.
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