The aim of this work was to establish the effect of dietary TFA and MSG on dyslipidemia, hepatic steatosis, and gene expression profile and to definitely assess the role of visceral white adipose tissue (WAT) in the pathogenesis of nonalcoholic fatty liver disease using an in vivo animal model. The amount of low-dose oral MSG used in this study (91 mg/kg bw) reflects current consumption levels (17, 18) and is 30�C40 times less than the level previously reported to induce neuronal damage when injected neonatally (13�C15). Since it has previously been suggested that MSG excitotoxicity occurs only when the blood brain barrier is vulnerable, for example, neonatally (15), we studied C57Bl/6J mice that had been bred and weaned from animals maintained on the respective diets for a 3-week run-in period prior to mating.

We analyzed hepatic and WAT microarray gene expression in order to gain insight into the commonalities and differences between the mechanism of TFA-induced steatosis versus that induced by MSG. To our knowledge, this is the first article to address the effect of these common food substances on hepatic and WAT gene expression in a rodent model of NAFLD. EXPERIMENTAL PROCEDURES Animals and diets C57BL/6J mice were from The Jackson Laboratory (Maine) and were housed/caged and fed a standard chow diet until 6 weeks of age, whereupon they were placed in one of four different dietary regimens for a period of 3 weeks prior to mating. The four diet regimens used in this study were as follows: 1) ad lib standard chow (control diet) with ad lib drinking water; 2) ad lib standard chow with ad lib drinking water containing 0.

64 g/l (91.2 �� 4.6 mg/kg bw):MSG(MSG diet); 3) ad lib test diet Purina 5001 with 20% (w/w) partially hydrogenated vegetable shortening [Test Diet #5C4M containing 8.68% (w/w) TFAs; Test Diet Purina] and ad lib drinking water (TFA diet); and [4] Diet #5C4M and Cilengitide ad lib drinking water containing 0.64 g/l (97 mg/kg bw) MSG (TFA+MSG diet). See Table 1 for diet composition. Following mating, the four groups of dams were maintained on their respective diets throughout the gestation and nursing period. Male offspring used in these experiments were weighed and then weaned onto the same diets and maintained in this regimen until they reached either 16 or 32 weeks of age. Average body weight and caliper girth was assessed at 6, 16, and 32 weeks of age; water intake and food consumption were assessed at 6 weeks and again at 28�C30 weeks. The breeding and care of the animals were in accordance with the protocols approved by the Animal Care and Use Committee of the King Faisal Specialist Hospital and Research Centre. TABLE 1.