Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high-fat and high-fructose diets

Jiung Pang Huang, Mei Ling Cheng, Cheng Yu Hung, Chao Hung Wang, Po Shiuan Hsieh, Ming Shi Shiao, Jan Kan Chen, Dai Er Li, Li Man Hung*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

18 Scopus citations


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.

Original languageEnglish
Pages (from-to)936-946
Number of pages11
JournalJournal of Diabetes
Issue number10
StatePublished - 10 2017

Bibliographical note

Publisher Copyright:
© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd


  • docosahexaenoic acid
  • docosapentaenoic acid
  • high-fat diet
  • high-fructose diet
  • insulin resistance


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