title: Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats.
abstract: BACKGROUND
  Apolipoprotein M (ApoM) is a constituent of high-density lipoproteins (HDL). It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels.
  
  
  OBJECTIVE
  To assess the effects of increased free fatty acids (FFAs) levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression.
  
  
  METHODS
  Adult male Sprague-Dawley (SD) rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR) were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK) rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array.
  
  
  RESULTS
  Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8) was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin.
  
  
  CONCLUSIONS
  These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.
authors.affiliation: Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Qinfeng
authors.initials: Q
authors.lastname: Mu
authors.affiliation: Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.affiliation: Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lunds University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Berggren-Söderlund
authors.affiliation: Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lunds University, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson-Ehle
authors.affiliation: Department of Cardiothoracic Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Luo
authors.affiliation: Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lunds University, Lund, Sweden.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism*; D000075243:Apolipoproteins M; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D054834:Lipocalins / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D054834:Lipocalins; D047494:PPAR delta; D048068:PPAR-beta; D012333:RNA, Messenger