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Article: High-fat diet consumption reduces hepatic folate transporter expression via nuclear respiratory factor-1
Title | High-fat diet consumption reduces hepatic folate transporter expression via nuclear respiratory factor-1 |
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Authors | |
Keywords | Folate High-fat diet Nuclear respiratory factor-1 Proton-coupled folate transporter Reduced folate carrier |
Issue Date | 2018 |
Publisher | Springer. The Journal's web site is located at http://www.springer.com/biomed/molecular/journal/109 |
Citation | Journal of Molecular Medicine, 2018, v. 96 n. 11, p. 1203-1213 How to Cite? |
Abstract | 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. |
Persistent Identifier | http://hdl.handle.net/10722/260562 |
ISSN | 2023 Impact Factor: 4.8 2023 SCImago Journal Rankings: 1.422 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Sid, V | - |
dc.contributor.author | Siow, YL | - |
dc.contributor.author | Shang, Y | - |
dc.contributor.author | Woo, WHC | - |
dc.contributor.author | O, K | - |
dc.date.accessioned | 2018-09-14T08:43:45Z | - |
dc.date.available | 2018-09-14T08:43:45Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Journal of Molecular Medicine, 2018, v. 96 n. 11, p. 1203-1213 | - |
dc.identifier.issn | 0946-2716 | - |
dc.identifier.uri | http://hdl.handle.net/10722/260562 | - |
dc.description.abstract | 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. | - |
dc.language | eng | - |
dc.publisher | Springer. The Journal's web site is located at http://www.springer.com/biomed/molecular/journal/109 | - |
dc.relation.ispartof | Journal of Molecular Medicine | - |
dc.rights | This is a post-peer-review, pre-copyedit version of an article published in Journal of Molecular Medicine. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00109-018-1688-8 | - |
dc.subject | Folate | - |
dc.subject | High-fat diet | - |
dc.subject | Nuclear respiratory factor-1 | - |
dc.subject | Proton-coupled folate transporter | - |
dc.subject | Reduced folate carrier | - |
dc.title | High-fat diet consumption reduces hepatic folate transporter expression via nuclear respiratory factor-1 | - |
dc.type | Article | - |
dc.identifier.email | Woo, WHC: cwhwoo@hku.hk | - |
dc.identifier.authority | Woo, WHC=rp01860 | - |
dc.description.nature | postprint | - |
dc.identifier.doi | 10.1007/s00109-018-1688-8 | - |
dc.identifier.scopus | eid_2-s2.0-85053399620 | - |
dc.identifier.hkuros | 290885 | - |
dc.identifier.volume | 96 | - |
dc.identifier.issue | 11 | - |
dc.identifier.spage | 1203 | - |
dc.identifier.epage | 1213 | - |
dc.identifier.isi | WOS:000448287300006 | - |
dc.publisher.place | Germany | - |
dc.identifier.issnl | 0946-2716 | - |