In this study, we explored the correlation between serum vitamin D concentrations and NAFLD in Chinese adults. We found that serum vitamin D concentrations of obese NAFLD patients were lower than those of obese controls without NAFLD. We also found that serum vitamin D concentrations were negatively correlated with the prevalence of NAFLD in obese but not lean participants. Our further analysis showed that decreased serum vitamin D concentrations or vitamin D deficiency were associated with an increased risk of NAFLD in obese but not lean participants. These findings suggested a significant correlation between serum vitamin D concentrations and NAFLD in obese but not lean participants.
Several studies have reported that there is a significant correlation between serum vitamin D concentrations and NAFLD (30, 31), and this was confirmed by a meta-analysis including 12794 participants of 17 studies (32). Moreover, low serum vitamin D concentrations are related to greater severity of hepatic steatosis and necrotizing inflammation both in children and in adults (33, 34). Preclinical investigations found that vitamin D supplementation significantly improved liver steatosis in high-fat diet-fed mice (35). Besides, we and others found that vitamin D receptor (VDR) is upregulated in the steatotic livers, and maybe a therapeutic target for NAFLD (35, 36). As we know, low serum vitamin D levels are more commonly observed in obese than in lean individuals (37). However, whether lean or obese individuals showed a similar association of vitamin D with NAFLD remains speculative and should be investigated. In this study, we provided evidence that low serum vitamin D levels were associated with obese but not lean populations.
The explanations for why obese and lean individuals have inconsistent correlations between vitamin D and NAFLD remains unclear, although several possibilities exist. First, obesity is closely associated with low vitamin D levels itself and maybe a major factor causing this result (38, 39). With fewer outdoor activities and low exposure to sunlight, obese individuals may have decreased vitamin D synthesized in the liver or percutaneously (8). A genetic study showed that each increase in BMI will reduce serum vitamin D concentration by 1.15% (40). Second, patients with vitamin D deficiency have higher serum levels of proinflammatory cytokines and promote the development of NAFLD (41). In the non-alcoholic steatohepatitis (NASH) stage, vitamin D deficiency can also actively regulate the synthesis of endogenous fatty acids in the liver by weakening the enterohepatic circulation (42). Third, vitamin D can increase the expression of peroxisome proliferator-activated receptor γ (PPAR-γ), thereby promoting the secretion of serum triglycerides and the accumulation of lipid droplets in hepatocytes (43). Therefore, under vitamin D deficiency conditions, the flow of free fatty acids (FFAs) in the blood increases, and fat deposition is accelerated into hepatocytes, contributing to the progress of NAFLD (44). Further researches are needed to clarify these possibilities.
Recently, researchers have subdivided NAFLD into obese and lean subtypes according to their obesity status, and many studies have focused on lean NAFLD (45–47). Vitamin D concentrations are closely related to NAFLD, and vitamin D deficiency is considered a risk factor for NAFLD (31, 44). However, it was not clear whether vitamin D concentrations were also associated with lean NAFLD. In this study, we found that low vitamin D concentrations are associated with obese but not lean NAFLD. Our results suggest that the vitamin D concentration may be an important predictor of NAFLD screening in obese but not lean population.
In this study, some limitations are acknowledged. First, our NAFLD was diagnosed based on ultrasound. Although ultrasound NAFLD diagnosis has been widely used clinically as a screening method for hepatic steatosis, it is still insufficient to detect mild steatosis and cannot replace the gold standard for liver biopsy. The correlation between vitamin D levels and NAFLD histological severity was not explored in this study. Second, this is a single-center cross-sectional study. Our sample size may be insufficient to represent the entire Chinese adult population, and further multi-center cohort studies are needed. Third, this study classified lean and obese participants by the BMI but did not include waist circumference or waist-to-hip ratio. It may mix some central obese patients with lean participants.