Serum, liver and bile sitosterol and sitostanol in obese patients with and without NAFLD

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. In addition, it has been suggested that the hepatic sterol transport mechanisms are altered in NAFLD. Therefore, we investigated the association between serum, liver and bile plant sterols and sitostanol with NAFLD.Methods: Out of the 138 individuals (age: 46.3 ± 8.9, body mass index: 43.3 ± 6.9 kg/m², 28% men and 72% women), 44 could be histologically categorized to have normal liver, and 94 to have NAFLD. Within the NAFLD group, 28 had simple steatosis and 27 had non-alcoholic steatohepatitis. Plant sterols and sitostanol were measured from serum (n=138), liver (n=38), and bile (n=41). The mRNA expression of genes regulating liver sterol metabolism and inflammation was measured (n=102).Results: Liver and bile sitostanol ratios to cholesterol were higher in those with NAFLD compared to those with histologically normal liver (all P<0.022). Furthermore, liver sitostanol to cholesterol ratio correlated positively with histological steatosis and lobular inflammation (rs > 0.407, P<0.01 for both). In contrast, liver sitosterol to cholesterol ratio correlated negatively with steatosis (rs = −0.392, P=0.015) and lobular inflammation (rs = −0.395, P=0.014). Transcriptomics analysis revealed suggestive correlations between serum plant sterol levels and mRNA expression.Conclusion: Our study showed that liver and bile sitostanol ratios to cholesterol associated positively and liver sitosterol ratio to cholesterol associated negatively with liver steatosis and inflammation in obese individuals with NAFLD..

Comment on Tauriainen et al.: Serum, liver and bile sitosterol and sitostanol in obese patients with and without NAFLD

“…To conclude, here we suggest the possibility that the observed finding by Tauriainen et al [ 1 ] regarding the positive association between sitostanol and lobular inflammation is likely to be a consequence of the applied analytical methodology.…”

“…In our hands, plasma and tissue concentrations for plant sterols as well as for stanols always shows a high correlation for all tissues analyzed, so also for liver, at least when measured via GC-MS. Therefore, the fact that Tauriainen et al [ 1 ] do find a correlation between hepatic and plasma sitosterol concentrations but not for sitostanol is again suggestive for a potential problem in their analysis of hepatic sitostanol via GC-FID.…”

“…However, in the paper by Tauriainen et al [ 1 ] there are some methodological issues that raise concerns, which we feel need to be addressed. First , while concentrations of three non-cholesterol sterols were reported, measurements of others like desmosterol, lathosterol, stigmasterol, and campestanol are missing.…”

“…In a previous issue of Bioscience Reports , Tauriainen et al [ 1 ] present data on the relations between serum, liver, and bile concentrations of sitosterol, campesterol, and sitostanol standardized for cholesterol in morbidly obese subjects with a normal liver or a fatty liver further subdivided into simple steatosis or NASH. In our opinion this is the first time that these non-cholesterol sterols have been reported in human liver samples – especially in conditions of a fatty liver compared with control – which is therefore of great scientific value.…”

“…Third , the authors concluded that hepatic sitosterol concentrations correlate negatively with steatosis and lobular inflammation, while sitostanol concentrations show a positive correlation with liver histology markers. However, we question whether these conclusions are correct since they are based on Spearman correlations (Table 2 in the original paper [ 1 ]). To our opinion, it is not appropriate to perform this analysis between continuous (plant sterol and stanol concentrations) and discrete variables (liver histology).…”