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

Abstract

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 -3 polyunsaturated fatty acid ( -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 PPAR -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.

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

“…High fat diets are generally related to obesity and insulin resistance (Buettner et al, 2006). In agreement with this, the present results show impaired glucose tolerance as evidenced by the higher AUC of the ipGTT and decreased hypothalamic InsR expression.…”

“…Our work demonstrates for the first time that if male rats consume phytoestrogens until they reach adult life, when the feed is replaced by a low phytoestrogen diet, an obese phenotype with alterations in glucose metabolism emerges. In fact, epididymal and perirenal fat pads were heavier and body weight was similar to rats fed a high saturated fat diet, which is widely known to induce marked weight gain (Buettner et al, 2006).…”

“…Considering reports that the absence of dietary phytoestrogens during pregnancy resulted in obesity during later adulthood in mice (Ruhlen et al, 2008), the last group was fed the same HP diet supplemented with 25 g of lard per 100 g of food as a source of dietary fat [high phytoestrogen-high fat (HP-HF)]. This has been widely reported as a useful model to induce obesity and metabolic syndrome (Buettner et al, 2006).…”

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

“…A high-fat diet has been used to induce obesity, dyslipidemia and IR in rodents for many decades. The complications developed by high-fat diet resemble human MS, and these complications may extend to cardiac hypertrophy, cardiac fibrosis, myocardial necrosis and hepatic steatosis [42][43][44][45] . In the present study, we found that after chronic stress, serum glucose and insulin concentrations and the IRI were significantly increased in male IUGR offspring, but the phenomenon failed to appear in IUGR females, indicating that the male offspring of PNE group presented hyperglycemia and IR.…”

Energy restriction ameliorates metabolic syndrome-induced cavernous tissue structural modifications in aged rats

“…Such HF diet, lard-derived, especially rich in saturated fatty acids, is recommended for induction of obesity-related metabolic changes, as dyslipidemia and insulin intolerance (Pajvani and Scherer 2003); it contrasts with diets containing fish oils, particularly rich in polyunsaturated ω-3 fatty acids, which have beneficial effects on body composition and insulin action (Buettner et al 2006). Beyond the ability to mimic human MetS, previous reports demonstrated that in rats, HF-fed related changes also extend to cardiovascular complications (Buettner et al 2006).…”