Abstract
BackgroundThe human diet has altered markedly during the past four decades, with the introduction of Trans hydrogenated fat, which extended the shelf-life of dietary oils and promoted a dramatic increase in elaidic acid (Trans-18.1) consumption. Food additives such as monosodium glutamate (MSG) and aspartame (ASP) were introduced to increase food palatability and reduce caloric intake. Nutrigenomics studies in small-animal models are an established platform for analyzing the interactions between various macro- and micronutrients. We therefore investigated the effects of changes in hepatic and adipose tissue gene expression induced by the food additives ASP, MSG or a combination of both additives in C57Bl/6 J mice fed a Trans fat-enriched diet.MethodsHepatic and adipose tissue gene expression profiles, together with body characteristics, glucose parameters, serum hormone and lipid profiles were examined in C57Bl/6 J mice consuming one of the following four dietary regimens, commencing in utero via the mother’s diet: [A] Trans fat (TFA) diet; [B] MSG + TFA diet; [C] ASP + TFA diet; [D] ASP + MSG + TFA diet.ResultsWhilst dietary MSG significantly increased hepatic triglyceride and serum leptin levels in TFA-fed mice, the combination of ASP + MSG promoted the highest increase in visceral adipose tissue deposition, serum free fatty acids, fasting blood glucose, HOMA-IR, total cholesterol and TNFα levels. Microarray analysis of significant differentially expressed genes (DEGs) showed a reduction in hepatic and adipose tissue PPARGC1a expression concomitant with changes in PPARGC1a-related functional networks including PPARα, δ and γ. We identified 73 DEGs common to both adipose and liver which were upregulated by ASP + MSG in Trans fat-fed mice; and an additional 51 common DEGs which were downregulated.ConclusionThe combination of ASP and MSG may significantly alter adiposity, glucose homeostasis, hepatic and adipose tissue gene expression in TFA-fed C57Bl/6 J mice.
Highlights
Obesity and nonalcoholic fatty liver disease (NAFLD) are comorbid conditions which are increasingly prevalent throughout the world [1]
Since Trans fat (TFA) [7,8,9,27], ASP [24] and monosodium glutamate (MSG) [9,21] have all been implicated in hepatic dysfunction, our aim was to examine the development of hepatic steatosis, adiposity and changes in hepatic and adipose tissue gene expression in response to ASP and MSG, or a combination of both, in animals maintained on a TFA -enriched diet
Livers presented with indications of micro- and macrosteatosis, with the ASP + MSG diet apparently resulting in the highest degree of overall steatosis compared to the other diet groups
Summary
Obesity and nonalcoholic fatty liver disease (NAFLD) are comorbid conditions which are increasingly prevalent throughout the world [1]. Increased abdominal adiposity has been shown to result from TFA-feeding in monkeys [7]; and increased visceral fat and hepatic lipid accumulation together with impaired insulin sensitivity were noted in rats consuming a low fat diet supplemented with 4.6% elaidic acid (Trans-18.1), which is the predominant lipid found in hydrogenated vegetable oils [8]. The human diet has altered markedly during the past four decades, with the introduction of Trans hydrogenated fat, which extended the shelf-life of dietary oils and promoted a dramatic increase in elaidic acid (Trans-18.1) consumption. Food additives such as monosodium glutamate (MSG) and aspartame (ASP) were introduced to increase food palatability and reduce caloric intake. We investigated the effects of changes in hepatic and adipose tissue gene expression induced by the food additives ASP, MSG or a combination of both additives in C57Bl/6 J mice fed a Trans fat-enriched diet
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