Silencing of FABP1 ameliorates hepatic steatosis, inflammation, and oxidative stress in mice with nonalcoholic fatty liver disease - PubMed (original) (raw)
Silencing of FABP1 ameliorates hepatic steatosis, inflammation, and oxidative stress in mice with nonalcoholic fatty liver disease
Takako Mukai et al. FEBS Open Bio. 2017.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide and has been identified as a risk factor for cirrhosis and hepatocellular carcinoma. However, there is no effective pharmacologic treatment for NAFLD. FABP1 is a liver-specific fatty acid-binding protein (FABP) that plays important roles in intracellular lipid metabolism in the liver. We investigated the effect of repression of FABP1 expression on NAFLD, using adenovirus-mediated silencing of FABP1. FABP1 knockdown in the liver decreased the liver weight and hepatic triglyceride (TG) accumulation. The expression of inflammatory and oxidative stress markers in the liver was also reduced. The level of thiobarbituric acid-reactive substances, a marker of lipid peroxidation, in the liver of FABP1 knockdown mice was significantly decreased. These results suggest that FABP1 reduction in the liver is an effective approach against NAFLD.
Keywords: FABP1; NAFLD.
Figures
Figure 1
Adenovirus‐mediated
FABP
1 knockdown in
HFD
‐fed C57
BL
/6J mice.
HFD
‐fed C57
BL
/6J mice were injected with Ad‐shLacZ or Ad‐sh
FABP
1 via the tail vein and killed 1 week later. (A) Real‐time
PCR
analysis of
FABP
1 expression in the liver. (B) Western blot analysis of
FABP
1 protein expression in the liver. The graph indicates the quantification of
FABP
1 protein. (C)
mRNA
expression of
FABP
family members was measured by real‐time
PCR
. Data are shown as the mean ±
SEM
(n = 7 per group). *P < 0.05, **P < 0.01.
Figure 2
Knockdown of
FABP
1 expression decreased liver weight and hepatic
TG
content.
HFD
‐fed C57
BL
/6J mice were injected with Ad‐shLacZ or Ad‐sh
FABP
1 via the tail vein (n = 7 per group). Mice were killed 1 week post injection. Liver weight (A, B), hepatic
TG
(C), and hepatic cholesterol (D) were determined. Data are shown as the mean ±
SEM
. *P < 0.05, ***P < 0.001. (E) Oil Red O staining and H&E staining of the liver in mice treated with Ad‐shLacZ or Ad‐sh
FABP
1. Scale bar, 100 μm.
Figure 3
FABP
1 knockdown attenuated hepatic fatty acid and
TG
synthesis. (A) Real‐time
PCR
analysis of genes involved in fatty acid oxidation and lipid synthesis in the liver of
HFD
‐fed C57
BL
/6J mice injected with Ad‐shLacZ or Ad‐sh
FABP
1. (B) Western blot analysis of
ACC
protein expression in the liver. The graph indicates the quantification of
ACC
protein. Data are presented as the mean ±
SEM
(n = 7 per group). *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 4
FABP
1 knockdown suppressed hepatic inflammation and oxidative stress. Real‐time
PCR
analysis of genes related to inflammation (A) and oxidative stress (B) in the liver of
HFD
‐fed C57
BL
/6J mice injected with Ad‐shLacZ or Ad‐sh
FABP
1. (C) Quantification of
TBARS
in the liver. Data are expressed as the mean ±
SEM
(n = 7 per group). *P < 0.05, **P < 0.01, ***P < 0.001.
References
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