title: Leptin-mediated inflammatory signaling crucially links visceral fat inflammation to obesity-associated β-cell dysfunction.
abstract: OBJECTIVE
  This study aimed to examine the causal relationship between adipokines released from visceral fat and pancreatic β-cell dysfunction in the state of obesity inflammation.
  
  
  METHODS
  Adipose tissue and adipocyte conditioned medium were obtained from epididymal fat of B6 mice on regular or high fat diet for 16 weeks. The latter were classified into two groups: overweight (OW, 40±2g) and obese (OB, 50±2g). Isolated mouse islets and NIT-1 cells were used to evaluate β-cell function.
  
  
  RESULTS
  Fasting glucose, leptin, and interleukin-6 levels were increased in OW mice and were further elevated in OB mice. Adipocyte size and number of adipose macrophage infiltrations showed a similar trend. The augmentation of homeostasis model assessment of insulin resistance, islet hyperplasia and macrophage infiltration was noted only in OB mice. The stimulation index was lower, but reactive oxygen species production was higher in islets isolated from OB mice than from controls. In epididymal fat conditioned medium, the increases in leptin, IL-6 and TNF-α production in OW mice were further elevated in OB mice except TNF-α. Adipose tissue conditioned medium suppressed the stimulation index of islets isolated from B6 mice but not from db/db mice. The suppressive effect was also reversed by co-treatment with N-acetylcysteine or NS-398 (a selective cyclooxygenase-2 inhibitor).
  
  
  CONCLUSIONS
  A markedly elevated leptin production from inflamed visceral fat could deteriorate β-cell function via leptin receptor-mediated oxidative stress and cyclooxygenase-2 activation in the development of obesity.
authors.affiliation: Division of General Surgery, Department of Surgery, Yung Kung Campus, Chi-Mei Medical Center, Tainan, Taiwan; Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Tian
authors.affiliation: Department of Physiology & Biophysics, National Defense Medical Center (NDMC), Taipei, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Family and Community Health, Tri-Service General Hospital, NDMC, Taipei, Taiwan.
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Loh
authors.affiliation: Department of Physiology & Biophysics, National Defense Medical Center (NDMC), Taipei, Taiwan; Department of Medical Research, Tri-Service General Hospital, Taipei, Taiwan. Electronic address: pshsieh@hotmail.com.
authors.forename: Po-Shiuan
authors.initials: PS
authors.lastname: Hsieh
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000503:physiopathology*; D050417:Insulin-Secreting Cells / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000503:physiopathology*; D050177:Overweight / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D054411:Receptors, Leptin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054392:Adipokines; D015850:Interleukin-6; D020738:Leptin; D054411:Receptors, Leptin; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D005947:Glucose
keywords: Adipose tissue inflammation; Leptin; Obesity; β-Cell dysfunction