Abstract:
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of hepatic metabolic perturbations
ranging from simple steatosis to steatohepatitis, cirrhosis and hepatocellular carcinoma. Currently,
lifestyle modifications to reduce weight gain are considered the most effective means of preventing
and treating the disease. The aim of the present study was to determine the therapeutic benefit of
Sclerocarya birrea (Marula leaf extract, MLE) on hepatic steatosis. Obese db/db mice were randomly
stratified into the obese control, metformin (MET) or MLE-treated groups. Mice were treated daily
for 29 days, at which point all mice were euthanized and liver samples were collected. Hematoxylin
and eosin staining was used for histological assessment of the liver sections, while qRT-PCR and
Western blot were used to determine hepatic mRNA and protein expression, respectively. Thereafter,
the association between methylenetetrahydrofolate reductase (Mthfr a key enzyme in one-carbon
metabolism and DNA-methylation-induced regulation of gene transcription) and lipogenic genes was
evaluated using Pearson’s correlation coefficient. Mice treated with MLE presented with significantly
lower body and liver weights as compared with the obese control and MET-treated mice (p ≤ 0.05).
Further, MLE treatment significantly inhibited hepatic steatosis as compared with the obese control
and MET-treated mice (p ≤ 0.05). The reduced lipid accumulation was associated with low expression
of fatty acid synthase (Cpt1; p ≤ 0.05) and an upregulation of the fatty acid oxidation gene, carnitine
palmitoyltransferase (Cpt1; p ≤ 0.01), as compared with the obese control mice. Interestingly, MLE
treatment improved the correlation between Mthfr and Cpt1 mRNA expression (r = 0.72, p ≤ 0.01).
Taken together, the results suggest that Marula leaf extracts may inhibit hepatic steatosis by influencing the association between Mthfr and genes involved in hepatic lipid metabolism. Further studies
are warranted to assess DNA methylation changes in lipid metabolism genes.
