Understanding the mechanisms that define the relationship between diet and physiology holds great promise to improve human health across the life-course. Indeed, nutrition has the potential to be the most significant, single primary prevention intervention in humans. However, progress towards this end has been impeded by the complex relationships between diet, physiology, development and ageing. Traditional approaches have usually focussed on ‘one-nutrient-at-a-time’ rather than considering the entire nutrient and dietary landscape. Here we have employed an integrative approach called the Geometric Framework for Nutrition (GFN) to explore in unprecedented detail the ways that nutrients and their interactions influence the multiple dimensions of phenotype (spanning molecular interactions to life-history traits) across life.
Male and female C57BL/6 mice were fed one of 18 diets differing systematically in protein, fat and carbohydrate content and energy density (n=9). Diet feeding was ad libitum for either 1, 6, 12 or 18 months. One week prior to cull, animals underwent physiological assessments including an oral glucose tolerance test (oGTT) and EchoMRI. At cull, tissues were processed and stored for later analysis. Proteomics analysis on liver was undertaken to assess the effects of dietary macronutrient intake across the life-course.
Broad level analysis shows that in mice, biological sex had the greatest variation in protein abundance in liver. Aging caused an upregulation in inflammatory pathways and downregulation in metabolism-related pathways including mitochondrial and amino acid metabolism. Clustering analysis shows that diet modulated the response and trajectory of the liver proteome with age.
These analyses indicate that the liver proteome is responsive to the influences of sex, diet and age. We are now harnessing the potential of this multidimensional study to delineate the differences in these interactions and their association with physiological parameters.