Serum folic acid levels are associated with the presence and severity of liver steatosis in Chinese adults

Xia, Mingfeng; Bian, Hua; Zhu, Xiaopeng; Yan, Hongmei; Chang, Xinxia; Zhang, Linshan; Hao, Lin; Hu, Xiaowen

doi:10.1016/j.clnu.2017.06.021

Cited by 33 publications

(27 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent study reported that patients with NAFLD had low serum folic acid levels, which was associated with severity of steatosis and hepatocellular ballooning (Xia et al 2018). In line with these clinical findings, the present study identified a low folate status that was associated with fatty liver caused by chronic consumption of a high-fat diet.…”

Section: Discussionsupporting

confidence: 87%

“…Obesity is a major risk factor of NAFLD. A previous study reported that low serum folate concentrations in obese patients directly correlated with increased severity of steatosis after adjusting for gender, age and BMI (Xia et al 2018). This suggests that low circulating folate levels might be an independent risk factor for NAFLD.…”

Section: Discussionmentioning

confidence: 91%

“…However, a low level of serum folates has been reported in patients with obesity, type 2 diabetes and NAFLD. Dysregulation of folate-dependent one-carbon metabolism has been implicated in NAFLD-related comorbidities such as obesity, type 2 diabetes, and metabolic syndrome (Mahabir et al 2008, da Silva et al 2014, Nilsson et al 2015, Xia et al 2018. Therefore, folic acid supplementation may be beneficial in patients with metabolic diseases such as obesity and NAFLD.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the implementation of mandatory folic acid fortification policy, dietary deficiency of folate is believed to be uncommon in generally healthy populations in Western countries (Bailey et al 2010, CDC 2010. However, despite adequate intake of folate from diets and supplements, obese individuals and patients with non-alcoholic fatty liver disease (NAFLD) are reported to have low folate levels in the circulation (Mojtabai 2004, Mahabir et al 2008, da Silva et al 2013, Xia et al 2018. In addition, low folate status is also observed in patients with malabsorption, impaired kidney function or liver disease, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Obesity is one of the most common risk factors for various chronic diseases (Must et al 2000). It has been reported that low levels of serum folate are associated with enhanced NAFLD severity in obese patients (Hirsch et al 2005, Xia et al 2018. However, the mechanism that leads to low folate status in obese patients is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Role of folate in nonalcoholic fatty liver disease

Sid

Siow

Karmin

2017

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Role of folate in nonalcoholic fatty liver disease

Sid

Siow

Karmin

2017

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

show abstract

Osteocalcin and Non-Alcoholic Fatty Liver Disease: Lessons From Two Population-Based Cohorts and Animal Models

Xia

Rong

Zhu

et al. 2020

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

Osteocalcin regulates energy metabolism in an active undercarboxylated/uncarboxylated form. However, its role on the development of non‐alcoholic fatty liver disease (NAFLD) is still controversial. In the current study, we investigated the causal relationship of circulating osteocalcin with NAFLD in two human cohorts and studied the effect of uncarboxylated osteocalcin on liver lipid metabolism through animal models. We analyzed the correlations of serum total/uncarboxylated osteocalcin with liver steatosis/fibrosis in a liver biopsy cohort of 196 participants, and the causal relationship between serum osteocalcin and the incidence/remission of NAFLD in a prospective community cohort of 2055 subjects from Shanghai Changfeng Study. Serum total osteocalcin was positively correlated with uncarboxylated osteocalcin (r = 0.528, p < .001). Total and uncarboxylated osteocalcin quartiles were inversely associated with liver steatosis, inflammation, ballooning, and fibrosis grades in both male and female participants (all p for trend <.05). After adjustment for confounding glucose, lipid, and bone metabolism parameters, the male and female participants with lowest quartile of osteocalcin still had more severe liver steatosis, with multivariate‐adjusted odds ratios (ORs) of 7.25 (1.07–49.30) and 4.44 (1.01–19.41), respectively. In the prospective community cohort, after a median of 4.2‐year follow‐up, the female but not male participants with lowest quartile of osteocalcin at baseline had higher risk to develop NAFLD (hazard ratio [HR] = 1.90; 95% confidence interval [CI] 1.14–3.16) and lower chance to achieve NAFLD remission (HR = 0.56; 95% CI 0.31–1.00). In wild‐type mice fed a Western diet, osteocalcin treatment alleviated hepatic steatosis and reduced hepatic SREBP‐1 and its downstream proteins expression. In mice treated with osteocalcin for a short term, hepatic SREBP‐1 expression was decreased without changes of glucose level or insulin sensitivity. When SREBP‐1c was stably expressed in a human SREBP‐1c transgenic rat model, the reduction of lipogenesis induced by osteocalcin treatment was abolished. In conclusion, circulating osteocalcin was inversely associated with NAFLD. Osteocalcin reduces liver lipogenesis via decreasing SREBP‐1c expression. © 2020 American Society for Bone and Mineral Research (ASBMR).

show abstract

High-fat diet consumption reduces hepatic folate transporter expression via nuclear respiratory factor-1

et al. 2018

View full text Add to dashboard Cite

Folate is an essential micronutrient for biological function. The liver, a primary organ for folate metabolism and storage, plays an important role in folate homeostasis. Proton-coupled folate transporter (PCFT) and reduced folate carrier (RFC) are the major folate transporters responsible for folate uptake at basolateral membrane of hepatocytes. Low serum folate levels are frequently associated with obesity. We investigated the mechanism that regulated folate status in a mouse model with diet-induced obesity. Mice (C57BL/6J) were fed a high-fat diet (60% kcal fat) for 8 weeks. Mice displayed increased hepatic lipid accumulation and decreased folate levels in the liver and serum compared to mice fed a normal chow diet (10% kcal fat). High-fat diet-fed mice had low expression of PCFT and RFC and decreased nuclear respiratory factor-1 (NRF-1)/DNA-binding activity. Treatment with NRF-1 siRNA or palmitic acid reduced folate transporter expression in hepatocytes. Inhibition of NRF-1 mediated folate transporter expression significantly reduced intracellular folate levels. These results suggest that chronic consumption of high-fat diets impairs folate transporter expression via NRF-1-dependent mechanism, leading to reduced hepatic folate storage. Understanding the regulation of folate homeostasis in obesity may have an important implication in current guideline of folate intake. KEY MESSAGES: Serum and liver folate levels are decreased in diet-induced obese mice. Chronic high-fat diet consumption impairs expression of hepatic PCFT and RFC. NRF-1 regulates hepatic folate transporters expression and folate levels.

show abstract

Serum folic acid levels are associated with the presence and severity of liver steatosis in Chinese adults

Cited by 33 publications

References 48 publications

Role of folate in nonalcoholic fatty liver disease

Role of folate in nonalcoholic fatty liver disease

Osteocalcin and Non-Alcoholic Fatty Liver Disease: Lessons From Two Population-Based Cohorts and Animal Models

High-fat diet consumption reduces hepatic folate transporter expression via nuclear respiratory factor-1

Contact Info

Product

Resources

About