Effect of Dietary Monosodium Glutamate on HFCS‐Induced Hepatic Steatosis: Expression Profiles in the Liver and Visceral Fat

Abstract

It has previously been shown that patients with nonalcoholic fatty liver disease (NAFLD) exhibit alterations in both hepatic and adipose tissue metabolism, and the dietary factors that contribute to the pathogenesis of NAFLD are likely to be multifactorial. Using C57BL/6J mice, we examined whether chronic exposure to low‐dose dietary monosodium glutamate (MSG), high‐fructose corn syrup (HFCS), or a combination of the two, vs. control would affect metabolism and hepatic and visceral fat gene expression in adult male progeny. A maternal diet containing 20% HFCS and/or dietary MSG (97.2 ± 6.3 mg/kg body weight (bw), provided in the drinking water) was offered ad libitum from 3 weeks before mating, and continued throughout gestation and weaning until the progeny reached 32 weeks of age. Liver and abdominal fat gene expression was compared with control animals fed isocaloric standard chow under identical conditions. HFCS induced hepatic steatosis and increased the expression of genes involved in carbohydrate and lipid metabolism. Conversely, dietary MSG elevated serum free fatty acids (FFAs), triglycerides (TGs), high‐density lipoprotein‐cholesterol (HDL‐C), and insulin, together with the expression of hepatic genes involved in lipid metabolism and bile synthesis. The HFCS+MSG combination elevated hepatic TGs, serum FFAs, and TG levels. In visceral white adipose tissue, both MSG and HFCS diets increased the expression of transcription factor Srebf2 and decreased expression of Ppargc1a, while downregulating the expression of mitochondrial respiratory chain components. MSG increased the expression of several genes implicated in adipocytes differentiation. We hypothesize that HFCS may promote hepatic steatosis, whereas dietary MSG induces dyslipidemia and markers of insulin resistance.

Nutrigenomics of hepatic steatosis in a feline model: effect of monosodium glutamate, fructose, and Trans-fat feeding

“…In humans, obesity is strongly associated with fatty liver disease that has been extensively studied in various rodent models of dietinduced NAFLD (Collison et al 2009a(Collison et al , 2010. Simple fatty liver disease is usually a benign condition; however, some individuals develop a progressively severe pathology involving fibrosis, inflammation, and cirrhosis, and the reason for this is not fully understood (Wouters et al Anstee and Goldin 2006;Ogasawara et al 2011).…”

“…Preliminary real-time RT-PCR experiments were performed with each primer pair to determine the annealing temperature that yielded the greatest amount of specific product with melting temperature (Tm) separable from primer dimer Tm. Standard curves were prepared for each run using known quantities of cDNA as described previously (Collison et al 2009a(Collison et al , 2010. Relative quantitation measurements were taken using external standard curves for both target and b-actin housekeeping gene.…”

“…Levels of hepatic TAG were quantified from snap-frozen tissue using the Triglyceride Determination Kit TRO100 with appropriate triacylglycerol standards (Sigma Aldrich, MO, USA) as described previously (Collison et al 2009a(Collison et al , 2010.…”

“…Several dietary macronutrients have been proposed to play a role in the development of hepatic steatosis (Lê and Bortolotti 2008), in particular a diet enriched with Trans-fat and a high fructose corn syrup (HFCS) equivalent was shown to promote severe NAFLD and hepatic necroinflammatory changes in rodents (Tetri et al 2008). Additionally, we have shown that Trans-fat (Collison et al 2009a) and HFCS (Collison et al 2010) alter rodent hepatic and white adipose tissue gene expression, promoting upregulation of lipogenic gene transcription and the deposition of hepatic TAG. The majority of research into the etiology and pathophysiology of hepatic steatosis has been performed using small animal models; however, rodent models of progressive diet-induced liver disease have been disappointing for a number of reasons (Larter and Yeh 2008;Anstee and Goldin 2006;Ogasawara et al 2011), and there is still a need for additional models that may contribute to our knowledge of the factors associated with the development of hepatic fibrosis and more severe associated pathology.…”

“…Our goal therefore was to compared the effects of four isocaloric diets on feline hepatic histology and gene expression, using a combination of partially hydrogenated vegetable shortening (PHVS) and HFCS to generate a Trans-fat (9%), HFCS (24%) diet. The effect of this diet was compared to an isocaloric standard chow, either in the presence or absence of dietary MSG (1.125%), in a model that we have previously established in rodents (Collison et al 2009a(Collison et al , 2010, and more recently in cats (Collison et al 2011). We bred our study animals from female cats who were previously established on these separate diets for 3 weeks prior to mating, since some of the effects of MSG are believed to occur only during the neonatal period (Alponti et al 2011;Roman-Ramos et al 2011;Hirata et al 1997;Diniz et al 2005;Matyšková 2008;Nemeroff et al 1978;Yu et al 1997), and because developmental programming of the metabolic syndrome may be affected by maternal nutritional balance (Armitage et al 2004;De Campos et al 2007).…”