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

• Published in: PloS one Vol. 5; no. 8; p. e12361
• Main Authors: Nookaew, Intawat, Gabrielsson, Britt G., Holmäng, Agneta, Sandberg, Ann-Sofie, Nielsen, Jens
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.08.2010; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipocytes, White - metabolism; Adipose tissue; Analysis; Animal tissues; Animals; Aorta; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Beef; Bioengineering; Biological effects; Biology; Biomedical data; Blood lipids; Body composition; Cardiovascular diseases; Chemical Sciences; Clustering; Computational Biology/Systems Biology; Computational Biology/Transcriptional Regulation; Consortia; Coronary vessels; Data processing; Diet; Engineering; Epidemics; Fatty acids; Fish oils; Fishes; Gene expression; Gene Expression Profiling; Genomes; Health care; Health care reform; Health risks; Influence; Kemi; Life sciences; Lipid metabolism; Lipids; Liver; Low density lipoprotein receptors; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Metabolic networks; Metabolic Networks and Pathways; Metabolism; Metabolites; methods; Mice; Musculoskeletal system; Nutrition research; Nutrition/Obesity; Obesity; Oil consumption; Ontology; Organ Specificity; Phenotype; Physiological aspects; Physiology; Protein synthesis; Protein turnover; Proteins; Proteins - metabolism; Receptor density; Rodents; Steroids (Organic compounds); Sterols; Sterols - metabolism; Studies; Sugar; Systems Biology; Systems Biology - methods; Tissue analysis; Transcription; White
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012361

Changes 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. Low-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. This 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.