High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

David Højland Ipsen, Pernille Tveden-Nyborg, Bidda Rolin, Günaj Rakipovski, Maria Beck, Line Winther Mortensen, Lasse Færk, Peter M. H. Heegaard, Peter Møller, Jens Lykkesfeldt

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    Abstract

    Background Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD. Methods Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high-fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 % cholesterol) for 16 and 25 weeks. Results All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001), LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p < 0.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p < 0.01) compared to control and vHS. Conclusion Collectively, our results suggest that intake of fat and cholesterol, but not sucrose, are the main factors driving the development and progression of dyslipidemia and NAFLD/NASH.
    Original languageEnglish
    Article number51
    JournalAnnals of Nutrition and Metabolism
    Volume13
    Number of pages10
    ISSN0250-6807
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Cholesterol
    • Dyslipidemia
    • Guinea pigs
    • High-fat diet
    • Non-alcoholic fatty liver disease
    • Non-alcoholic steatohepatitis
    • Sucrose

    Cite this

    Ipsen, David Højland ; Tveden-Nyborg, Pernille ; Rolin, Bidda ; Rakipovski, Günaj ; Beck, Maria ; Mortensen, Line Winther ; Færk, Lasse ; Heegaard, Peter M. H. ; Møller, Peter ; Lykkesfeldt, Jens. / High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs. In: Annals of Nutrition and Metabolism. 2016 ; Vol. 13.
    @article{028ae6e3a9f34351b953296e9d139227,
    title = "High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs",
    abstract = "Background Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD. Methods Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 {\%} fat), a very high-sucrose diet (vHS: 4 {\%} fat, 25 {\%} sucrose), a high-fat diet (HF: 20 {\%} fat, 0.35 {\%} cholesterol), a high-fat/high-sucrose diet (HFHS: 20 {\%} fat, 15 {\%} sucrose, 0.35 {\%} cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 {\%} fat, 25 {\%} sucrose, 0.35 {\%} cholesterol) for 16 and 25 weeks. Results All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001), LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p < 0.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p < 0.01) compared to control and vHS. Conclusion Collectively, our results suggest that intake of fat and cholesterol, but not sucrose, are the main factors driving the development and progression of dyslipidemia and NAFLD/NASH.",
    keywords = "Cholesterol, Dyslipidemia, Guinea pigs, High-fat diet, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Sucrose",
    author = "Ipsen, {David H{\o}jland} and Pernille Tveden-Nyborg and Bidda Rolin and G{\"u}naj Rakipovski and Maria Beck and Mortensen, {Line Winther} and Lasse F{\ae}rk and Heegaard, {Peter M. H.} and Peter M{\o}ller and Jens Lykkesfeldt",
    year = "2016",
    doi = "10.1186/s12986-016-0110-1",
    language = "English",
    volume = "13",
    journal = "Annals of Nutrition and Metabolism",
    issn = "0250-6807",
    publisher = "S. Karger AG",

    }

    High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs. / Ipsen, David Højland; Tveden-Nyborg, Pernille; Rolin, Bidda; Rakipovski, Günaj; Beck, Maria; Mortensen, Line Winther; Færk, Lasse; Heegaard, Peter M. H.; Møller, Peter ; Lykkesfeldt, Jens.

    In: Annals of Nutrition and Metabolism, Vol. 13, 51, 2016.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

    AU - Ipsen, David Højland

    AU - Tveden-Nyborg, Pernille

    AU - Rolin, Bidda

    AU - Rakipovski, Günaj

    AU - Beck, Maria

    AU - Mortensen, Line Winther

    AU - Færk, Lasse

    AU - Heegaard, Peter M. H.

    AU - Møller, Peter

    AU - Lykkesfeldt, Jens

    PY - 2016

    Y1 - 2016

    N2 - Background Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD. Methods Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high-fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 % cholesterol) for 16 and 25 weeks. Results All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001), LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p < 0.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p < 0.01) compared to control and vHS. Conclusion Collectively, our results suggest that intake of fat and cholesterol, but not sucrose, are the main factors driving the development and progression of dyslipidemia and NAFLD/NASH.

    AB - Background Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD. Methods Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high-fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 % cholesterol) for 16 and 25 weeks. Results All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001), LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p < 0.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p < 0.01) compared to control and vHS. Conclusion Collectively, our results suggest that intake of fat and cholesterol, but not sucrose, are the main factors driving the development and progression of dyslipidemia and NAFLD/NASH.

    KW - Cholesterol

    KW - Dyslipidemia

    KW - Guinea pigs

    KW - High-fat diet

    KW - Non-alcoholic fatty liver disease

    KW - Non-alcoholic steatohepatitis

    KW - Sucrose

    U2 - 10.1186/s12986-016-0110-1

    DO - 10.1186/s12986-016-0110-1

    M3 - Journal article

    C2 - 27512407

    VL - 13

    JO - Annals of Nutrition and Metabolism

    JF - Annals of Nutrition and Metabolism

    SN - 0250-6807

    M1 - 51

    ER -