title: Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high-fat and high-fructose diets.
abstract: BACKGROUND
  The aim of the present study was to compare insulin resistance and metabolic changes using a global lipidomic approach.
  
  
  METHODS
  Rats were fed a high-fat diet (HFD) or a high-fructose diet (HFrD) for 12 weeks to induce insulin resistance (IR) syndrome. After 12 weeks feeding, physiological and biochemical parameters were examined. Insulin sensitivity and plasma metabolites were evaluated using a euglycemic-hyperinsulinemic clamp and mass spectrometry, respectively. Pearson's correlation coefficient was used to investigate the strength of correlations.
  
  
  RESULTS
  Rats on both diets developed IR syndrome, characterized by hypertension, hyperlipidemia, hyperinsulinemia, impaired fasting glucose, and IR. Compared with HFrD-fed rats, non-esterified fatty acids were lower and body weight and plasma insulin levels were markedly higher in HFD-fed rats. Adiposity and plasma leptin levels were increased in both groups. However, the size of adipocytes was greater in HFD- than HFrD-fed rats. Notably, the lipidomic heat map revealed metabolites exhibiting greater differences in HFD- and HFrD-fed rats compared with controls. Plasma adrenic acid levels were higher in HFD- than HFrD-fed rats. Nevertheless, linoleic and arachidonic acid levels decreased in HFrD-fed rats compared with controls. Plasma concentrations of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were significantly reduced after feeding of both diets, particularly the HFrD. There was a strong positive correlation between these two fatty acids and the insulin sensitivity index.
  
  
  CONCLUSIONS
  The systemic lipidomic analysis indicated that a reduction in DHA and DPA was strongly correlated with IR in rats under long-term overnutrition. These results provide a potential therapeutic target for IR and metabolic syndrome.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jiung-Pang
authors.initials: JP
authors.lastname: Huang
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan.|Division of Cardiology, Department of Internal Medicine, Heart Failure Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Cheng
authors.affiliation: Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Hung
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Heart Failure Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Po-Shiuan
authors.initials: PS
authors.lastname: Hsieh
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Shiao
authors.affiliation: Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan.|Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jan-Kan
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Dai-Er
authors.initials: DE
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan.|Division of Cardiology, Department of Internal Medicine, Heart Failure Center, Chang Gung Memorial Hospital, Keelung, Taiwan.|Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Li-Man
authors.initials: LM
authors.lastname: Hung
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates; D004281:Docosahexaenoic Acids / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005632:Fructose; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004040:Dietary Carbohydrates; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D005632:Fructose; C026219:docosapentaenoic acid
keywords: docosahexaenoic acid; docosapentaenoic acid; high-fat diet; high-fructose diet; insulin resistance; 二十二碳六烯酸; 二十碳五烯酸; 胰岛素抵抗; 高果糖饮食; 高脂肪饮食