BUETTNER, ROLAND, JÜ RGEN SCHÖ LMERICH, AND L. CORNELIUS BOLLHEIMER. High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity. 2007;15:798 -808. Research Methods and Procedures: High-fat (HF) diet feeding can induce obesity and metabolic disorders in rodents that resemble the human metabolic syndrome. However, this dietary intervention is not standardized, and the HF-induced phenotype varies distinctly among different studies. The question which HF diet type is best to model the metabolic deterioration seen in human obesity remains unclear. Therefore, in this review, metabolic data obtained with different HF diet approaches are compiled. Both whole-body and organ-specific diet effects are analyzed. Results: On the basis of these results, we conclude that animal fats and -6/ -9-containing plant oils can be used to generate an obese and insulin-resistant phenotype in rodents, whereas fish oil-fed animals do not develop these disorders. Discussion: Looking at the present data, it does not seem possible to define an ideal HF diet, and an exact definition of diet composition and a thorough metabolic characterization of the HF diet effects in a researcher's specific laboratory setting remains essential for metabolic studies with this model.

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.

Summary To study the effects of fatty acids and the involvement of the Toll‐like receptor‐4/nuclear factor‐κB (TLR‐4/NF‐κB) pathway with respect to the secretion of adipokines from adipocytes 3T3‐L1 adipocytes were stimulated with increasing doses of fatty acids. The secretion of adiponectin, resistin and monocyte chemoattractant protein‐1 (MCP‐1) was measured by enzyme‐linked immunosorbent assay. The NF‐κB p65 nuclear translocation and TLR‐4 expression were investigated by Western blot. The effects mediated by NF‐κB were tested using a specific NF‐κB‐inhibitor and TLR‐4‐induced effects were analysed with a neutralizing TLR‐4 antibody. Binding of 14C‐labelled fatty acids to TLR‐4/MD‐2 was investigated using a FLAG‐tagged extracellular part of TLR‐4 fused to full‐length MD‐2 via a linker (lipopolysaccharide‐Trap). The messenger RNA (mRNA) expression of adipokines in abdominal adipose tissue of rats fed a standard chow or a high‐fat diet was investigated by reverse transcription–polymerase chain reaction. The TLR‐4 is induced during adipocyte differentiation and its expression is enhanced following fatty acid stimulation. The stimulatory effects of stearic and palmitic acids on MCP‐1 secretion and of palmitoleic acid on resistin secretion are mediated via NF‐κB. The stimulatory effects of stearic, palmitic and palmitoleic acids on resistin secretion and the stimulatory effect of stearic acid on MCP‐1 secretion are mediated via TLR‐4. Fatty acid‐mediated effects are caused by an endogenous ligand because fatty acids were shown not to bind directly to TLR‐4/MD‐2. Adipose tissue mRNA expression and serum levels of adipokines did not differ in rats fed a high‐fat diet. These data provide a new molecular mechanism by which fatty acids can link nutrition with innate immunity.

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Objective: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated. Methods: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available. Results: SF values were significantly increased in men and women with high BMI (. 25 kg/m 2 ), increased cholesterol (. 200 mg/dl), and increased systolic (. 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (. 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF. Conclusions: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS.European Journal of Endocrinology 154 333-340