Blood Lipid Responses to Diet (BoLD)

The macronutrient composition of our diet (proportions of carbohydrates, fats and proteins) strongly influences the way our body stores and utilises substrates (e.g., fats and sugars), which in turn influences our risk of developing cardiometabolic diseases (e.g., coronary artery disease or insulin resistance). The optimal dietary composition to lower the risk of cardiometabolic disease is unknown. In a randomized, parallel design, this study will investigate how the overconsumption of carbohydrates and fats affects blood lipid responses and liver metabolism in adults free from metabolic disease.

Dietary and lifestyle interventions are central to lowering the risk and preventing the development of metabolic disease, including non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. There is, however, no one fits all dietary approach, and in the context of diets where an individual is not gaining or losing weight (known as eucaloric), the optimal macronutrient composition associated with a reduced risk of metabolic disease and dyslipidemia is highly debated. For instance, eating less of one macronutrient implies eating more of another; a reduction in the intake of dietary carbohydrates is met by an increase in dietary fats. How this affects one's metabolic health in the setting when someone is not gaining or losing body weight is unclear. Therefore, this study aims to provide an understanding of the effect that the quantity of specific dietary macronutrients (e.g., carbohydrates, fats) have on plasma triglyceride concentrations in both the fasting and postprandial state, liver fat content and metabolism, and cardiac fat content and function. Sixty volunteers free from metabolic disease will be recruited into a randomized, parallel-armed dietary intervention study. Participants will consume either a low carbohydrate, high-fat diet or a high carbohydrate, low-fat diet for up to 28 days. Diets will be eucaloric (i.e., designed to meet the individual participant's energy requirements). Comprehensive in vivo metabolic and physiological testing will be performed before and after the experimental diet to document the effects of the overconsumption of specific macronutrients (i.e., fats or carbohydrates) on liver and lipid metabolism.

Eucaloric diet enriched in either carbohydrates or fat (both contributing to 65% total energy intake)

Change in plasma triglyceride concentrations in response to consumption of macronutrient meal will be measured by basic clinical chemistry before and at the end of the dietary intervention.

Liver fat content (intra-hepatic triglyceride) will be measured before and at the end of the dietary intervention by magnetic resonance imaging/spectroscopy

Cardiac fat content will be measured before and at the end of the dietary intervention by magnetic resonance imaging/spectroscopy

Change in the contribution of dietary and adipose tissue derived fatty acids to very low density lipoprotein-triglyceride (VLDL-TG) palmitate

Through measuring the incorporation of [13C]palmitate and [2H2]palmitate in isolated plasma VLDL during a mixed-macronutrient feeding test.

Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study. Male or Female, aged ≥18 to ≤65 years Body mass index (BMI) ≥19 to ≤35 kg/m2 No medical condition or relevant drug therapy that is known to affect the liver, adipose tissue, or cardiac metabolism. Weight stable for the previous 3 months Exclusion Criteria: Aged <18 or >65 years BMI <19 or >35 kg/m2 A blood haemoglobin <135 mg/dL for men and <120 mg/dL for women Donated (or lost) ≥250 mL of blood in the previous two months On a weight loss diet or decreased their body weight by >5% in the previous 3 months Currently adhering to or have consumed in the previous 3 months a diet with a notably altered macro-nutrient content (e.g. high-fat - low-carbohydrate diet) Have increased their body weight by >5% in the previous 3 months Any metabolic condition or relevant drug therapy Current smoker History of alcoholism or a greater than recommended alcohol intake (>30 g of alcohol daily for men and >20 g of alcohol daily for women) History of albumin allergy. Pregnant or nursing mothers History of severe claustrophobia