FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1963645707> ?p ?o ?g. }

• W1963645707 endingPage "1267" @default.
• W1963645707 startingPage "1255" @default.
• W1963645707 abstract "Excessive production of triglyceride-rich very low-density lipoproteins (VLDL-TG) contributes to hypertriglyceridemia in obesity and type 2 diabetes. To understand the underlying mechanism, we studied hepatic regulation of VLDL-TG production by (forkhead box O6) FoxO6, a forkhead transcription factor that integrates insulin signaling to hepatic metabolism. We showed that transgenic mice expressing a constitutively active FoxO6 allele developed hypertriglyceridemia, culminating in elevated VLDL-TG levels and impaired postprandial TG clearance. This effect resulted in part from increased hepatic VLDL-TG production. We recapitulated these findings in cultured HepG2 cells and human primary hepatocytes, demonstrating that FoxO6 promoted hepatic VLDL-TG secretion. This action correlated with the ability of FoxO6 to stimulate hepatic production of microsomal triglyceride transfer protein (MTP), a molecular chaperone that catalyzes the rate-limiting step in VLDL-TG assembly and secretion. FoxO6 was shown to bind to the MTP promoter and stimulate MTP promoter activity in HepG2 cells. This effect was inhibited by insulin, consistent with the ability of insulin to promote FoxO6 phosphorylation and disable FoxO6 DNA-binding activity. Mutations of the FoxO6 target site within the MTP promoter abrogated FoxO6-mediated induction of MTP promoter activity. Hepatic FoxO6 expression became deregulated in insulin-resistant mice with obesity and type 2 diabetes. FoxO6 inhibition in insulin-resistant liver suppressed hepatic MTP expression and curbed VLDL-TG overproduction, contributing to the amelioration of hypertriglyceridemia in obese and diabetic db/db mice. These results characterize FoxO6 as an important signaling molecule upstream of MTP for regulating hepatic VLDL-TG production." @default.
• W1963645707 created "2016-06-24" @default.
• W1963645707 creator A5002611263 @default.
• W1963645707 creator A5012550408 @default.
• W1963645707 creator A5014061259 @default.
• W1963645707 creator A5028889627 @default.
• W1963645707 creator A5029523959 @default.
• W1963645707 creator A5035023285 @default.
• W1963645707 creator A5063090617 @default.
• W1963645707 creator A5067775249 @default.
• W1963645707 creator A5078122670 @default.
• W1963645707 creator A5088174174 @default.
• W1963645707 date "2014-04-01" @default.
• W1963645707 modified "2023-10-14" @default.
• W1963645707 title "FoxO6 Integrates Insulin Signaling With MTP for Regulating VLDL Production in the Liver" @default.
• W1963645707 cites W1569851802 @default.
• W1963645707 cites W1978677356 @default.
• W1963645707 cites W1988731412 @default.
• W1963645707 cites W2000223380 @default.
• W1963645707 cites W2005112725 @default.
• W1963645707 cites W2007887164 @default.
• W1963645707 cites W2008688211 @default.
• W1963645707 cites W2011523747 @default.
• W1963645707 cites W2025201486 @default.
• W1963645707 cites W2026887934 @default.
• W1963645707 cites W2028551167 @default.
• W1963645707 cites W2034751031 @default.
• W1963645707 cites W2045918150 @default.
• W1963645707 cites W2048580400 @default.
• W1963645707 cites W2048910934 @default.
• W1963645707 cites W2051781840 @default.
• W1963645707 cites W2056388945 @default.
• W1963645707 cites W2070752858 @default.
• W1963645707 cites W2074345254 @default.
• W1963645707 cites W2076103389 @default.
• W1963645707 cites W2078176020 @default.
• W1963645707 cites W2078524991 @default.
• W1963645707 cites W2083775524 @default.
• W1963645707 cites W2089085210 @default.
• W1963645707 cites W2097089354 @default.
• W1963645707 cites W2107188599 @default.
• W1963645707 cites W2111546385 @default.
• W1963645707 cites W2112021284 @default.
• W1963645707 cites W2116461852 @default.
• W1963645707 cites W2120177943 @default.
• W1963645707 cites W2123521914 @default.
• W1963645707 cites W2125481927 @default.
• W1963645707 cites W2129722153 @default.
• W1963645707 cites W2130610669 @default.
• W1963645707 cites W2133620886 @default.
• W1963645707 cites W2135569210 @default.
• W1963645707 cites W2136229559 @default.
• W1963645707 cites W2137506791 @default.
• W1963645707 cites W2138349577 @default.
• W1963645707 cites W2140566574 @default.
• W1963645707 cites W2142842603 @default.
• W1963645707 cites W2144970509 @default.
• W1963645707 cites W2158686289 @default.
• W1963645707 cites W2162943945 @default.
• W1963645707 cites W2164454326 @default.
• W1963645707 cites W2314427600 @default.
• W1963645707 cites W394964229 @default.
• W1963645707 cites W4237731298 @default.
• W1963645707 cites W4244189832 @default.
• W1963645707 cites W4254146802 @default.
• W1963645707 cites W4255925138 @default.
• W1963645707 doi "https://doi.org/10.1210/en.2013-1856" @default.
• W1963645707 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3959596" @default.
• W1963645707 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24437489" @default.
• W1963645707 hasPublicationYear "2014" @default.
• W1963645707 type Work @default.
• W1963645707 sameAs 1963645707 @default.
• W1963645707 citedByCount "29" @default.
• W1963645707 countsByYear W19636457072012 @default.
• W1963645707 countsByYear W19636457072015 @default.
• W1963645707 countsByYear W19636457072016 @default.
• W1963645707 countsByYear W19636457072017 @default.
• W1963645707 countsByYear W19636457072018 @default.
• W1963645707 countsByYear W19636457072019 @default.
• W1963645707 countsByYear W19636457072020 @default.
• W1963645707 countsByYear W19636457072021 @default.
• W1963645707 countsByYear W19636457072022 @default.
• W1963645707 countsByYear W19636457072023 @default.
• W1963645707 crossrefType "journal-article" @default.
• W1963645707 hasAuthorship W1963645707A5002611263 @default.
• W1963645707 hasAuthorship W1963645707A5012550408 @default.
• W1963645707 hasAuthorship W1963645707A5014061259 @default.
• W1963645707 hasAuthorship W1963645707A5028889627 @default.
• W1963645707 hasAuthorship W1963645707A5029523959 @default.
• W1963645707 hasAuthorship W1963645707A5035023285 @default.
• W1963645707 hasAuthorship W1963645707A5063090617 @default.
• W1963645707 hasAuthorship W1963645707A5067775249 @default.
• W1963645707 hasAuthorship W1963645707A5078122670 @default.
• W1963645707 hasAuthorship W1963645707A5088174174 @default.
• W1963645707 hasBestOaLocation W19636457071 @default.
• W1963645707 hasConcept C112446052 @default.
• W1963645707 hasConcept C126322002 @default.
• W1963645707 hasConcept C13028836 @default.

• next