title: Role of leptin on the expression of low density lipoprotein receptor.
abstract: OBJECTIVE
  Leptin resistance oriented hyperleptinaemia is a common problem in obese subjects in association with hypercholesterolaemia. The most common target for hypercholesterolaemia is impaired low density lipoprotein receptor (LDLR). This study was carried out to investigate whether any alteration in LDLR expression could explain the occurrence of hypercholesterolaemia in the event of hyperleptinaemia.
  
  
  METHODS
  Expression of LDLR and SREBP2 (sterol regulatory element binding protein 2) were examined in HepG2 cells by RT-PCR and Western blotting. JAK2 inhibitor II was used to verify the effect of JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway (common mediator for cytokine signaling). Co-localization of LDLR and insulin receptor (IR) was examined by confocal microscopy.
  
  
  RESULTS
  Leptin was found to reduce the expression of LDLR and its transcription factor SREBP2. On the other hand, a weak signal for stimulation of LDLR by leptin was noted to be mediated by JAK2 pathway. But the joint effect of the two signaling pathways kept LDLR only in depressed mode in presence of leptin. Confocal microscopy showed that LDLR made an intensively co-localized complex with insulin receptor in presence of leptin.
  
  
  CONCLUSIONS
  Our results show that though leptin stimulates LDLR expression very weakly through JAK-STAT signaling pathway, it mainly imposes inhibition on LDLR expression by inhibiting transcription factor SREBP2. The inter-association between LDLR and IR may be a reason to render LDLR functionally inactive in presence of leptin.
authors.forename: Naval Kishor
authors.initials: NK
authors.lastname: Yadav
authors.forename: Albina
authors.initials: A
authors.lastname: Arjuman
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Nimai C
authors.initials: NC
authors.lastname: Chandra
mesh_terms: D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism* / Q000473:pathology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D020738:Leptin / Q000008:administration & dosage* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D011972:Receptor, Insulin / Q000378:metabolism; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2
chemical_list: D020738:Leptin; D011973:Receptors, LDL; C497390:SREBF2 protein, human; D050791:STAT Transcription Factors; D051782:Sterol Regulatory Element Binding Protein 2; D011972:Receptor, Insulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2