title: Roux-en-Y gastric bypass improves hepatic mitochondrial function in obese rats.
abstract: BACKGROUND
  Obesity-related fatty liver disease is linked to mitochondrial dysfunction and oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates mitochondrial function and is a transcriptor of multiple genes that produce antioxidants. Because Roux-en-Y gastric bypass (RYGB) improves fatty liver and decreases the oxidative stress in the liver, we hypothesized that RYGB activates Nrf2 and increases cytochrome C oxidase subunit II (COX-II) in the liver of obese rats.
  
  
  METHODS
  Sprague-Dawley rats were fed a high-fat diet for 16 weeks. The obese rats underwent either RYGB (n = 20) or a sham operation (n = 20). The tissues were harvested 13 weeks postoperatively. The nuclear fraction and mitochondrial extracts were used for protein analysis with immunoblotting. Immunostaining was done on liver sections for COX-II, Nrf2, and the macrophage marker ED2 and F4/80. The gels were quantified using densitometry; P ≤ .05 was considered significant.
  
  
  RESULTS
  RYGB increased COX-II expression in the liver sections (3330 ± 56 versus 2056 ± 37 for RYGB versus sham, P < .001). The total (nuclear and cytoplasmic) Nrf2 expression was high in the obese sham-operated control (2456 ± 45 versus 4352 ± 76, RYGB versus sham, P < .001). However, the nuclear fraction of Nrf2 was significantly increased in the RYGB liver (2341 ± 46 versus 1352 ± 35, RYGB versus sham, P < .001). Furthermore, Nrf2 protein co-localized with the molecular markers of Kupffer cells.
  
  
  CONCLUSIONS
  Diet-induced fatty liver is associated with mitochondrial dysfunction. RYGB increases COX-II, which is involved in mitochondrial respiration, and increases the nuclear translocation of the Nrf2 transcriptional factor, which is involved in mitochondrial biogenesis and function. Taken together, these data suggest that surgically induced weight loss is associated with improved mitochondrial function in obese rats.
authors: James A. Haley Veterans Affairs Medical Center, Department of Surgery, University of South Florida, Tampa, FL 33601, USA.
authors: Yanhua
authors: Y
authors: Peng
authors: Michel M
authors: MM
authors: Murr
mesh_terms: D000818:Animals; D051381:Rats; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism; D015390:Gastric Bypass; D007728:Kupffer Cells / Q000378:metabolism; D008930:Mitochondria, Liver / Q000502:physiology; D028361:Mitochondrial Diseases / Q000209:etiology / Q000503:physiopathology; D009765:Obesity / Q000378:metabolism / Q000601:surgery; D018384:Oxidative Stress / Q000502:physiology; D017207:Rats, Sprague-Dawley; D015431:Weight Loss / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV; D051267:NF-E2-Related Factor 2