Ahmed Mohamed Ben-Amer, Nawal and Buyong, Zunariah and Abdullah, Nor Zamzila and Hamdan, Asmah Hanim and Ab Rahman, Jamalludin and Kuttulebbai Naina Mohamed Salam, Sirajudeen
(2023)
Retinoic acid targeting DGAT2 in non-alcoholic
fatty liver disease model.
Medicine & Health, 18 (7 (Suppl)).
p. 140.
E-ISSN 2289-5728
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) is caused by triglyceride
(TG) accumulation in the hepatocyte. The initial reversible stage is steatosis, and if
left untreated may progress to steatohepatitis, marked by necrosis and inflammation,
eventually leading to cirrhosis. Currently, there are no approved therapeutics for
NAFLD. Retinoic acid (RA), the active form of vitamin A, has been found to be
reduced in individuals with NAFLD and animal models have shown that RA could
mitigate TG accumulation in the liver. However, the mechanism of RA’s action
remains to be determined. Diacylglycerol acyltransferase (DGAT) catalyzes the
final step in triglyceride synthesis in the liver. We aimed to evaluate the effect of
RA on hepatic expression of DGAT2 in diet induced NAFLD rats. Materials and
Methods: NAFLD was induced through a high cholesterol diet (HCD). Thirty-six
rats were divided into four groups; a control group with a normal diet, HCD group
treated with a vehicle, HCD group and a HCD group that received subcutaneous
RA twice weekly for four weeks. The percentage of steatosis, ballooning and
inflammation of the livers were compared between groups. Immunohistochemistry
hepatic DGAT2 expression was determined using Image J software. The findings
were analysed using one-way ANOVA followed by the post hoc Scheffe test.
Results: The administration of RA significantly reduced TG accumulation in the
liver. We observed improvement in steatosis (48.6+9.8 vs 22.1+12.4, P<0.001),
ballooning, and inflammation in the livers of HCD group receiving RA compared
to HCD group. The results also demonstrated a significant (P<0.0001) decrease in
expression of DGAT2 enzyme in the liver of HCD animals received RA (12.1+1.8)
when compared to animals with HCD only (21.5+1.9). Conclusion: These findings
reveal the potential therapeutic efficacy of RA in improving NAFLD possibly via
inhibiting DGAT2.
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