title: Long-term High-fat High-sucrose Diet Promotes Enlarged Islets and β-Cell Damage by Oxidative Stress in Bama Minipigs.
abstract: OBJECTIVE
  The effect of a long-term high-fat, high-caloric diet on the dysfunction of pancreas has not been clarified. We investigated the pancreatic histopathology and β-cell apoptosis in Bama minipigs after 23 months on a high-fat high-sucrose diet (HFHSD).
  
  
  METHODS
  Bama minipigs were randomly assigned to control (n = 6) and HFHSD groups (n = 6) for 23 months, and biochemical parameters were measured. Pancreata were subjected to histological analysis, followed by assessment with transmission electron microscopy. Lipid peroxidation was determined by the malondialdehyde concentration and antioxidant enzyme activity. Β-cell apoptosis was measured by an immunohistochemical method.
  
  
  RESULTS
  In the HFHSD group, the islets were enlarged, and the pancreatic tissue had observed significant fatty infiltration. Moreover, the feeding program damaged the normal pancreatic tissue structure. The level of lipid peroxidation was increased, and the activities of pancreatic antioxidant enzymes were significantly decreased. The expression levels of caspase-3, Bax, and insulin were significantly increased (P < 0.05), and the expression levels of proliferating cell nuclear antigen and Bcl-2 were decreased (P < 0.05).
  
  
  CONCLUSIONS
  The long-term HFHSD promotes pancreatic steatosis and oxidative stress, which increases β-cell apoptosis as indicated by the activation of caspase-3 through the mitochondrial pathway (Bcl-2/Bax).
authors.affiliation: From the *State Key Laboratory of Animal Nutrition, Department of Gene and Cell Engineering, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences; and †Department of Veterinary Anatomy, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Zhan-zhao
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Lei-lei
authors.initials: LL
authors.lastname: Xin
authors.forename: Ji-han
authors.initials: JH
authors.lastname: Xia
authors.forename: Shu-lin
authors.initials: SL
authors.lastname: Yang
authors.forename: Yao-xing
authors.initials: YX
authors.lastname: Chen
authors.forename: Kui
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D059305:Diet, High-Fat; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D006003:Glycogen / Q000378:metabolism; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000648:ultrastructure; D007515:Islets of Langerhans / Q000378:metabolism* / Q000648:ultrastructure; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010182:Pancreatic Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; D019422:Dietary Sucrose; D007328:Insulin; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D006003:Glycogen; D053148:Caspase 3