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

May 25, 2006Journal of molecular endocrinology

Metabolic and molecular effects of different fat types in high-fat diet rat models

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Abstract

Male Wistar rats fed a high-fat diet comprising lard or olive oil exhibited significant obesity and insulin resistance.

Different high-fat diets resulted in distinct metabolic outcomes in rodents.
Rats on lard (HF-L) and olive oil (HF-O) diets showed pronounced obesity and insulin resistance.
Diets rich in coconut fat (HF-C) and fish oil (HF-F) maintained near-normal insulin sensitivity.
Elevated plasma levels of omega-3 polyunsaturated fatty acids were observed in HF-F fed rats.
Liver histology revealed hepatic steatosis in HF-L, HF-O, and HF-C diets without major inflammation.
SREBP1c-dependent genes were upregulated in response to HF-L and HF-O, while PPARalpha-dependent genes were upregulated in HF-F.

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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 omega-3 polyunsaturated fatty acid (omega-3-PUFA) and saturated fatty acid (C(12)-C(14), 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 PPARalpha-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.

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

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