title: Potential involvement of JNK1 repression in the hepatic effect of sitagliptin and metformin in rats subjected to high fat diet and chronic mild distress.
abstract: BACKGROUND
  Depression and non-alcoholic steatohepatitis (NASH) are highly co-morbid, and hepatic JNK pathway may be involved in their relation.
  
  
  OBJECTIVE
  To evaluate the impact of depression on NASH through the involvement of JNK1 and to assess the effect of sitagliptin and metformin on hepatic JNK1 expression in both NASH and NASH associated with depression.
  
  
  METHODS
  Eight groups of male Wistar rats were used: naïve rats, non-stressed NASH, non-stressed NASH sitagliptin treated, non-stressed NASH metformin treated, stressed, stressed NASH untreated, stressed NASH sitagliptin treated and stressed NASH metformin treated. Behavioral, biochemical, molecular and histopathological studies were performed.
  
  
  RESULTS
  Non-stressed NASH group showed depressive like symptoms, disturbed glucose homeostasis, impairment of liver functions, decrease adiponectin and increase malondialdehyde, which were aggreviated by stress. Sitagliptin produced significant improvement compared to metformin regarding biochemical and histopathological parameters. Furthermore, sitagliptin significantly decreased expression of hepatic JNK1 in both stressed and non-stressed rats. All these changes were accompanied by significant improvement of behavioral changes.
  
  
  CONCLUSIONS
  The link between NASH and depression raised the role of JNK activation through increase expression of JNK1. Since sitagliptin was associated with preferable effects than metformin, therefore, it is potentially preferred in the management of either NASH or NASH associated with depression.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: y_yosra@hotmail.com.
authors.forename: Yosra M
authors.initials: YM
authors.lastname: Magdy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: omnyah2011@gmail.com.
authors.forename: Omnyah A
authors.initials: OA
authors.lastname: El-Kharashi
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: enassamer@hotmail.com.
authors.forename: Enas S
authors.initials: ES
authors.lastname: Nabih
authors.affiliation: Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: safashalaby@yahoo.com.
authors.forename: Safaa M
authors.initials: SM
authors.lastname: Shaker
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: lobna-pharma@hotmail.com.
authors.forename: Lobna F
authors.initials: LF
authors.lastname: Abd-Elaziz
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: sawsanaf2005@yahoo.com.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Aboul-Fotouh
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D003863:Depression / Q000097:blood / Q000201:enzymology* / Q000523:psychology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000068900:Sitagliptin Phosphate / Q000494:pharmacology*; D013315:Stress, Psychological / Q000097:blood / Q000201:enzymology* / Q000523:psychology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D008687:Metformin; D048055:Mitogen-Activated Protein Kinase 8; D000068900:Sitagliptin Phosphate
keywords: Behavior; Chronic restraint stress; Depression; JNK; Metformin; NASH; Rat; Sitagliptin