The
protein level of human hepatitis B virus (HBV) in
infection is variable, depending on patient context. We previously reported that
HBV X protein (HBx) induces hepatic
lipid accumulation and
inflammation. Here, we show that abnormal levels of hepatic
fatty acids increase HBx protein stability during HBV expression, resulting in the potentiation of HBx-induced
inflammation.
Reactive oxygen species, Ca(2+) signaling and expression levels of various
lipid metabolic genes were investigated in HBx-expressing cells and in HBx transgenic mice.
Fatty acids, including
palmitate,
stearate and
oleate, increased HBx protein stability by preventing
proteasome-dependent degradation. Hepatic
inflammation induced by a high fat diet (HFD) and HBx was measured based on the expression of
interleukin-6 and
tumor necrosis factor α. In addition, the
protein level of HBx increased in HFD-HBx transgenic mice.
Reactive oxygen species production and intracellular Ca(2+) signal activation play critical roles in
fatty-acid-induced HBx stabilization. Abnormal levels of hepatic
fatty acids resulted in synergistic induction of HBx
protein and liver inflammatory gene expression through HBx
protein stabilization. These results indicate that different
fatty acid levels in the liver might affect HBV-induced pathogenesis.