title: Diet-induced obesity associated with steatosis, oxidative stress, and inflammation in liver.
abstract: BACKGROUND
  Obesity induces steatosis and increases oxidative stress, as well as chronic inflammation in the liver. The balance between lipogenesis and lipolysis is disrupted in obese animals. At a cellular level, the changes in metabolic sensors and energy regulators are poorly understood. We hypothesized that diet-induced steatosis increases oxidative stress, inflammation, and changes the metabolic regulators to promote energy storage in mice. The setting was a university-affiliated basic science research laboratory.
  
  
  METHODS
  Four-week-old C57BL mice were fed a high-fat diet (n = 8) or regular chow (n = 8) for 7 weeks. The liver sections were stained for fat content and immunofluorescence. Liver homogenates were used for protein analysis by immunoblotting and mRNA analysis by reverse transcriptase-polymerase chain reaction. The gels were quantified using densitometry P ≤ .05 was considered significant.
  
  
  RESULTS
  The high-fat diet upregulated protein kinase-C atypical isoforms ζ and λ and decreased glucose tolerance and the interaction of insulin receptor substrate 2 with phosphoinositide kinase-3. The high-fat diet increased the transcriptional factors liver X receptor (4321 ± 98 versus 2981 ± 80) and carbohydrate response element-binding protein (5132 ± 135 versus 3076 ± 91), the lipogenesis genes fatty acid binding protein 5, stearoyl-co-enzyme A desaturase-1, and acetyl-co-enzyme A carboxylase protein, and fatty acid synthesis. The high-fat diet decreased 5'-adenosine monophosphate-activated protein kinase (2561 ± 78 versus 1765 ± 65), glucokinase-3β (2.214 ± 34 versus 3356 ± 86), and SIRT1 (2015 ± 76 versus 3567 ± 104) and increased tumor necrosis factor-α (3415 ± 112 versus 2042 ± 65), nuclear factor kappa B (5123 ± 201 versus 2562 ± 103), cyclooxygenase-2 (4230 ± 113 versus 2473 ± 98), nicotinamide-adenine dinucleotide phosphate oxidase (3501 ± 106 versus 1600 ± 69) and reactive oxygen species production (all P < .001, obese mice versus lean mice).
  
  
  CONCLUSIONS
  A high-fat diet impairs glucose tolerance and hepatic insulin signaling, upregulates transcriptional and translational activities that promote lipogenesis, cytokine production, proinflammatory signaling, and oxidative stress, and downregulates lipolysis. Understanding the complex cellular signals triggered by obesity might have profound clinical implications.
authors: Department of Surgery, James A. Haley Veterans Affairs Medical Center, University of South Florida, Tampa, Florida, USA.
authors: Yanhua
authors: Y
authors: Peng
authors: Drew
authors: D
authors: Rideout
authors: Steven
authors: S
authors: Rakita
authors: James
authors: J
authors: Lee
authors: Michel
authors: M
authors: Murr
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D004032:Diet; D059305:Diet, High-Fat; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005234:Fatty Liver / Q000209:etiology*; D047468:Immunoprecipitation; D007249:Inflammation / Q000209:etiology; D007328:Insulin / Q000032:analysis; D008103:Liver Cirrhosis / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics; D009765:Obesity / Q000150:complications* / Q000235:genetics; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D019014:fas Receptor / Q000235:genetics
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C082667:Fabp5 protein, mouse; C491899:Fas protein, mouse; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D019014:fas Receptor; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D000594:Amino Acid Oxidoreductases; C059460:1-aminocyclopropane-1-carboxylic acid oxidase