title: Alleviating VLDL overproduction is an important mechanism for Laminaria japonica polysaccharide to inhibit atherosclerosis in LDLr-/-mice with diet-induced insulin resistance.
abstract: The overproduction of very low density lipoprotein (VLDL) is an important cause for initiation and development of atherosclerosis, which is highly associated with insulin signaling. The aim of this work is to verify whether the inhibition of VLDL overproduction is an underlying mechanism for a Laminaria japonica polysaccharide (LJP61A (where LJP is L. japonica)) to resist atherosclerosis.
  
  
  
  LJP61A (50 and 200 mg/kg/day) was orally administered to a high-fat diet (HFD)-fed LDL receptor deficient mice for 14 weeks. LJP61A significantly attenuated insulin resistance, hepatic steatosis, atherosclerosis, and dyslipidemia. Meanwhile, LJP61A ameliorated the HFD-induced impairment of hepatic insulin signaling and reduced VLDL overproduction via regulating the expression of genes involved in the assembly and secretion of VLDL. To study the possibility that the inhibition of mammalian target of rapamycin complex 1 and stimulation of Forkhead box protein O1 (Foxo1) nuclear exclusion is a result of LJP61A via regulating insulin signaling, LJP61A was administrated to HepG2 cells in the presence or absence of mTOR inhibitor and Foxo1 inhibitor. Results showed that LJP61A alleviated VLDL overproduction via regulating insulin receptor substrate mediated phosphatidylinositide 3-kinase AKT mammalian target of rapamycin complex 1 and phosphatidylinositide 3-kinase AKT-Foxo1 signaling pathways.
  
  
  
  These results suggested that LJP61A ameliorated HFD-induced insulin resistance to attenuate VLDL overproduction possibly via regulating insulin signaling, leading to the inhibition of atherosclerosis.
authors.affiliation: School of Biological and Medical Engineering, Hefei University of Technology, Hefei, China.|School of Food Science and Engineering, Hefei University of Technology, Hefei, China.
authors.forename: Xue-Qiang
authors.initials: XQ
authors.lastname: Zha
authors.affiliation: School of Food Science and Engineering, Hefei University of Technology, Hefei, China.
authors.forename: Wei-Nan
authors.initials: WN
authors.lastname: Zhang
authors.affiliation: School of Food Science and Engineering, Hefei University of Technology, Hefei, China.
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Peng
authors.affiliation: School of Food Science and Engineering, Hefei University of Technology, Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.affiliation: School of Biological and Medical Engineering, Hefei University of Technology, Hefei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Food Science and Engineering, Hefei University of Technology, Hefei, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Luo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D007795:Laminaria / Q000737:chemistry*; D008079:Lipoproteins, VLDL / Q000032:analysis; D008297:Male; D051379:Mice; D011134:Polysaccharides / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D007328:Insulin; C573412:LDLR protein, human; D008079:Lipoproteins, VLDL; D011134:Polysaccharides; D011973:Receptors, LDL; C435941:INSR protein, human; D011972:Receptor, Insulin
keywords: Atherosclerosis; Insulin resistance; Laminaria japonica; Polysaccharide; Very low density lipoprotein