title: Deficiency in Nrf2 transcription factor decreases adipose tissue mass and hepatic lipid accumulation in leptin-deficient mice.
abstract: OBJECTIVE
  To evaluate whether Nrf2 deficiency impacts insulin resistance and lipid accumulation in liver and white adipose tissue.
  
  
  METHODS
  Lep(ob/ob) mice (OB) with targeted Nrf2 deletion (OB-Nrf2KO) were generated. Pathogenesis of obesity and type 2 diabetes was measured in C57BL/6J, Nrf2KO, OB, and OB-Nrf2KO mice. Hepatic lipid content, lipid clearance, and very low-density lipoprotein (VLDL) secretion were determined between OB and OB-Nrf2KO mice.
  
  
  RESULTS
  OB-Nrf2KO mice exhibited decreased white adipose tissue mass and decreased adipogenic and lipogenic gene expression compared with OB mice. Nrf2 deficiency prolonged hyperglycemia in response to glucose challenge, which was paralleled by reduced insulin-stimulated Akt phosphorylation. In OB mice, Nrf2 deficiency decreased hepatic lipid accumulation, decreased peroxisome proliferator-activated receptor γ expression and nicotinamide adenine dinucleotide phosphate (NADPH) content, and enhanced VLDL secretion. However, this observation was opposite in lean mice. Additionally, OB-Nrf2KO mice exhibited increased plasma triglyceride content, decreased HDL-cholesterol content, and enhanced apolipoprotein B expression, suggesting Nrf2 deficiency caused dyslipidemia in these mice.
  
  
  CONCLUSIONS
  Nrf2 deficiency in Lep(ob/ob) mice reduced white adipose tissue mass and prevented hepatic lipid accumulation but induced insulin resistance and dyslipidemia. This study indicates a dual role of Nrf2 during metabolic dysregulation-increasing lipid accumulation in liver and white adipose tissue but preventing lipid accumulation in obese mice.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, USA; Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang, People's Republic of China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Xu
authors.forename: Ajay C
authors.initials: AC
authors.lastname: Donepudi
authors.forename: Vijay R
authors.initials: VR
authors.lastname: More
authors.forename: Supriya R
authors.initials: SR
authors.lastname: Kulkarni
authors.forename: Liya
authors.initials: L
authors.lastname: Li
authors.forename: Liangran
authors.initials: L
authors.lastname: Guo
authors.forename: Bingfang
authors.initials: B
authors.lastname: Yan
authors.forename: Tapan
authors.initials: T
authors.lastname: Chatterjee
authors.forename: Neal
authors.initials: N
authors.lastname: Weintraub
authors.forename: Angela L
authors.initials: AL
authors.lastname: Slitt
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D007333:Insulin Resistance; D020738:Leptin / Q000172:deficiency*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D020738:Leptin; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D014157:Transcription Factors