title: Transcriptional activation of apolipoprotein CIII expression by glucose may contribute to diabetic dyslipidemia.
abstract: OBJECTIVE
  Hypertriglyceridemia and fatty liver are common in patients with type 2 diabetes, but the factors connecting alterations in glucose metabolism with plasma and liver lipid metabolism remain unclear. Apolipoprotein CIII (apoCIII), a regulator of hepatic and plasma triglyceride metabolism, is elevated in type 2 diabetes. In this study, we analyzed whether apoCIII is affected by altered glucose metabolism.
  
  
  RESULTS
  Liver-specific insulin receptor-deficient mice display lower hepatic apoCIII mRNA levels than controls, suggesting that factors other than insulin regulate apoCIII in vivo. Glucose induces apoCIII transcription in primary rat hepatocytes and immortalized human hepatocytes via a mechanism involving the transcription factors carbohydrate response element-binding protein and hepatocyte nuclear factor-4α. ApoCIII induction by glucose is blunted by treatment with agonists of farnesoid X receptor and peroxisome proliferator-activated receptor-α but not liver X receptor, ie, nuclear receptors controlling triglyceride metabolism. Moreover, in obese humans, plasma apoCIII protein correlates more closely with plasma fasting glucose and glucose excursion after oral glucose load than with insulin.
  
  
  CONCLUSIONS
  Glucose induces apoCIII transcription, which may represent a mechanism linking hyperglycemia, hypertriglyceridemia, and cardiovascular disease in type 2 diabetes.
authors.affiliation: University Lille Nord de France, Lille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caron
authors.forename: An
authors.initials: A
authors.lastname: Verrijken
authors.forename: Ilse
authors.initials: I
authors.lastname: Mertens
authors.forename: Carolina Huaman
authors.initials: CH
authors.lastname: Samanez
authors.forename: Gisèle
authors.initials: G
authors.lastname: Mautino
authors.forename: Joel T
authors.initials: JT
authors.lastname: Haas
authors.forename: Daniel
authors.initials: D
authors.lastname: Duran-Sandoval
authors.forename: Janne
authors.initials: J
authors.lastname: Prawitt
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Vallez
authors.forename: Anne
authors.initials: A
authors.lastname: Muhr-Tailleux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berard
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Sudha B
authors.initials: SB
authors.lastname: Biddinger
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Luc
authors.initials: L
authors.lastname: Van Gaal
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
mesh_terms: D000328:Adult; D000818:Animals; D053305:Apolipoprotein C-III / Q000097:blood / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D050171:Dyslipidemias / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000819:agonists / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000819:agonists / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D053305:Apolipoprotein C-III; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001786:Blood Glucose; D005947:Glucose; D006360:Heat-Shock Proteins; D051557:Hepatocyte Nuclear Factor 4; D007328:Insulin; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011972:Receptor, Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C496592:HNF4A protein, human; C116385:MLXIPL protein, human; C442825:Mlxipl protein, rat; C486497:PPARGC1A protein, human; C501429:Ppargc1a protein, rat