Identifying Molecular Effects of Diet through Systems Biology: Influence of Herring Diet on Sterol Metabolism and Protein Turnover in Mice

Abstract

BackgroundChanges in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD). This will require methods for linking nutrient intake with specific metabolic processes in different tissues.Methodology/Principal FindingLow-density lipoprotein receptor-deficient (Ldlr −/−) mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice.ConclusionThis study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity.

Unraveling Molecular Signatures of Immunostimulatory Adjuvants in the Female Genital Tract through Systems Biology

“…This integrated approach has been recently used to identify the molecular effects of diet on metabolism in mice [27]. An intriguing finding that emerged from our integrated analysis was the co-expression of genes involved in proteasome activation and MHC class I peptide loading in the vagina of mice given CpG ODN or α-GalCer.…”

Mapping Condition-Dependent Regulation of Lipid Metabolism inSaccharomyces cerevisiae

“…Notably, our results suggest that Upc2p functions by controlling the enzyme levels at the transcriptional level and that this results in altered fluxes toward ergosterol. This points to Upc2p playing a similar function as the SREBP-1 transcription factor in mammals (Nielsen 2009; Nookaew et al 2010). Our analysis also identified a significant link between ergosterol and 1-acyl-sn-glycerol-3-phosphate acyltransferase ( SLC1 ), which is responsible for the synthesis of phosphatidic acid (PA).…”

Dietary herring improves plasma lipid profiles and reduces atherosclerosis in obese low-density lipoprotein receptor-deficient mice

“…This proposed synergy effect between taurine and long-chain n-3 PUFA, present in herring but not in beef muscle, could be an explanation to the finding of maintained HDL-cholesterol and lower VLDL-cholesterol concentrations in the herring-fed mice. In the transcriptome study performed on a subset of the mice (n=3 per diet group) we found that hepatic Cyp7a1 transcript levels were higher in the herring-fed compared with the beef-fed mice (24). That Cyp7a1 is a promising candidate as a mediator for the herring-induced effects is supported by the finding that Ldlr -/-mice overexpressing Cyp7a1 were resistant to diet-induced hypercholesterolemia (40).…”

“…The present study shows the physiological effects of dietary herring vs. beef on body composition, adipocyte size, lipid profiles and atherosclerosis. Transcriptome data derived from a subset of these animals (n=3 per diet group) has previously been published (24).…”