Defining high-fat-diet rat models: metabolic and molecular effects of different fat types

    1. R Buettner,
    2. K G Parhofer1,
    3. M Woenckhaus2,
    4. C E Wrede,
    5. L A Kunz-Schughart1,
    6. J Schölmerich and
    7. L C Bollheimer
    1. Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany
    2. 1Department of Internal Medicine II–Großhadern, University of Munich, 81377 München, Germany
    3. 2Department of Pathology, University of Regensburg, 93042 Regensburg, Germany
    1. (Requests for offprints should be addressed to R Buettner; Email: roland.buettner{at}


    High-fat (HF)-diet rodent models have contributed significantly to the analysis of the pathophysiology of the insulin resistance syndrome, but their phenotype varies distinctly between different studies. Here, we have systematically compared the metabolic and molecular effects of different HF with varying fatty acid compositions. Male Wistar rats were fed HF diets (42% energy; fat sources: HF-L – lard; HF-O – olive oil; HF-C – coconut fat; HF-F – fish oil). Weight, food intake, whole-body insulin tolerance and plasma parameters of glucose and lipid metabolism were measured during a 12-week diet course. Liver histologies and hepatic gene expression profiles, using Affymetrix GeneChips, were obtained. HF-L and HF-O fed rats showed the most pronounced obesity and insulin resistance; insulin sensitivity in HF-C and HF-F was close to normal. Plasma ω-3 polyunsaturated fatty acid (ω-3-PUFA) and saturated fatty acid (C12-C14, SFA) levels were elevated in HF-F and HF-C animals respectively. The liver histologies showed hepatic steatosis in HF-L, HF-O and HF-C without major inflammation. Hepatic SREBP1c-dependent genes were upregulated in these diets, whereas PPARα-dependent genes were predominantly upregulated in HF-F fed rats. We detected classical HF effects only in diets based on lard and olive oil (mainly long-chain, saturated (LC-SFA) and monounsaturated fatty acids (MUFA)). PUFA- or MC-SFA-rich diets did not induce insulin resistance. Diets based on LC-SFA and MUFA induced hepatic steatosis with SREBP1c activation. This points to an intact transcriptional hepatic insulin effect despite resistance to insulin’s metabolic actions.

    • Revision received 28 January 2006
    • Accepted 22 February 2006
    • Made available online as an Accepted Preprint 27 February 2006
    • Accepted Preprint first posted online on 27 February 2006
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