Short Oral Presentation Nutrition Society of Australia 50th Annual Scientific Meeting 2026

How does dietary macronutrient composition across the lifespan influence the cardiac proteome in male and female mice? (147014)

Meng Yuan 1 2 , Amanda Brandon 1 2 3 , Tamara Pulpitel 1 2 , Ella Meares 1 , Yasemin Ismail 1 , Flora Mackay 1 2 , Carsten Schmitz-Peiffer 1 2 , Lewin Small 1 2 , Alistair Senior 1 2 , Sophie Stonehouse 1 2 , Letisha Prescott 1 2 , Alyssa Face 1 2 , K. Saiful Islam 1 2 , David Raubenheimer 1 2 , Gregory J Cooney 1 2 , David G Le Couteur 1 3 4 , Stephen Simpson 1 2
  1. Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
  2. School of Life and Environmental Science, The University of Sydney, Sydney, NSW, 2006, Australia
  3. ANZAC Research Institute, Concord Hospital and Faculty of Medicine and Health, Sydney, NSW 2139, Australia
  4. School of Medical Sciences, Faculty of Medicine and Health, Sydney, NSW, Australia

Ageing is a fundamental biological process characterized by the progressive accumulation of molecular and cellular damage, ultimately leading to increased risk of chronic diseases, including cardiometabolic diseases. Calorie restriction, Mediterranean, plant-based and Dietary Approaches to Stop Hypertension (DASH) diets are widely recognized for their effectiveness in preventing cardiac diseases [1]. These diets are characterized by high levels of unsaturated fats and fibre, along with varying proportions of macronutrients, which help regulate blood pressure, lipid and glucose levels. However, the relationship between macronutrient composition, cardiometabolic health and longevity is complex, context-dependent, and may not be uniformly beneficial across different populations, life stages, and environmental settings [2].Traditional dietary interventions usually focus on ‘one-nutrient-at-a-time’ approach rather than considering the entire nutrient landscape. In the current study, we employed the Geometric Framework for Nutrition (GFN) to explore the ways that macronutrients and their interactions influence the multiple dimensions of phenotype across life, specifically focusing here on cardiac-metabolic health. Male and female C57BL/6 mice were fed one of 18 diets differing systematically in protein, fat and carbohydrate content and energy density. Diet was provided ad libitum for either 1, 6, 12 or 18 months. One week prior to cull, animals underwent an oral glucose tolerance test (oGTT) and EchoMRI. At cull, heart and other tissues were collected and stored for later analysis. Proteomic analysis was performed on the heart to assess the effects of dietary macronutrient intake across the life-course between sexes. There were effects of diet, sex and age on body mass and heart weight (p<0.001). Basal glucose and adiposity were also affected by diet, sex and age (p<0.001), with carbohydrate intake driving these phenotypes in the early timepoints in females. Heart proteomics showed that Pdk4, a key regulator of cardiac glucose, fatty acid substrate utilization and a potential indicator of development cardiomyopathy, was positively associated with fat intake. Acot1, which is potentially protective against CVD, showed a negative relationship with carbohydrate intake. Acox1 involved in peroxisomal β-oxidation, was upregulated in protein and fat intake. These analyses indicate that mouse phenotypes and cardiac proteomics are responsive to sex, diet and age. We are now harnessing the potential of identifying nutrient-responsive cardiac pathway for supporting cardiometabolic health during ageing.

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