There is little doubt scientifically that healthy eating, such as adhering to the Mediterranean diet (MedDiet) principles, is key for the prevention of cardiovascular disease (CVD). There is also convincing evidence for a strong inverse relationship between moderate intensity physical activity (PA) and mortality. Surprisingly, no study has yet formally documented how the combination of a MedDiet and regular PA improves cardiometabolic health in high-risk individuals. Why is this an important issue to address? On the one hand, a rigorous demonstration that the combination of a healthy diet and PA is better than the sum of each part in terms of cardiometabolic benefits will underpin the importance of advocating the combination of both modalities systematically to maximize health effects. Alternatively (and provocatively), results showing that healthy eating and PA have non-additive or non-synergistic effects will imply that one needs to adhere to only one of these two lifestyle modalities to maximizes cardiometabolic benefits. The overarching aim of this research is to test the hypothesis that consumption of a MedDiet combined with PA do act synergistically to improve cardiometabolic risk. The investigators hypothesize that healthy eating and PA act in synergy to reduce postprandial lipemia, a powerful independent risk factor for coronary heart disease.

This is a randomized study with a 2X2 experimental factorial design. A total of 200 men and women recruited in the Quebec City area via various media will participate in this study. Eligible participants will be randomly assigned to one of four 16-week intervention groups: 1- Mediterranean Diet (MedDiet); 2- Physical Activity (PA); 3- Combination of MedDiet and PA; 4- Control Group. Depending on the group, the intervention involves support for nutritional and PA components at different times, in groups or individually. The subjects assigned to the MedDiet will receive certain foods each week to enhance adherence to the diet. Subjects assigned to the PA groups will have the opportunity to have one to two practices supervised by week by a team kinesiologist. All participants will have questionnaires to complete at different times during the study. These questionnaires will document several important aspects of the study including participants' health status, eating behaviours, hunger and satiety levels, eating and PA habits, motivation levels and well-being. Participants' diets will be assessed using a validated web 24-hour recall (R24W), which evaluates the food and beverages consumed during the 24 hours prior to the day they complete the questionnaire. This questionnaire will be completed over three randomly selected days on five occasions during the study. The level of PA will be evaluated using an accelerometer that objectively calculates energy expenditure. This device will be worn by participants for consecutive periods of 7 days, 5 times during the study.

Serum triglycerides (TG) concentrations after an oral fat load (35g of fat/m2 of body surface) and other the outcome variables will be measured in each group at baseline and at the end of the 16-week intervention. Specially, the fat load test will occur 2 days after the end of the intervention (114 days), so that the effect of the last exercise training bout has washed out. Cardiometabolic risk factors in the fasting state will be measured at baseline as well as twice at the end of the intervention, i.e. at 16 weeks (112 days) and at 16.3 weeks (114 days). The cardiorespiratory condition of the subjects will be evaluated during an maximal exercise test at the beginning and end of the 16-week intervention (112 days). Body composition will be assessed at the beginning and end of the intervention (112 days) by Dual Energy X-ray Absorptiometry (DEXA). Cardiac structure and function will be measured at the beginning and end (112 days) of the intervention using advanced echocardiographic imaging. Exercise capacity (VO2max) will measured by a modified Bruce protocol at the beginning and end (112 days) of the intervention. Fecal sample will be collected as an optional part of the study at baseline as well as at the end of the intervention (112 days). Deep 16S rDNA metagenomic analysis (in feces) as well as analyses of microbiota metabolites and endogenous bioactive lipid mediators in plasma will be used as surrogates of gut microbiota composition and function.

The primary objective is to compare the impact of each intervention and hence the potential synergistic impact of the MedDiet and PA on postprandial TG concentrations measured 4 hours after consumption of the oral fat load.

Secondary objectives are to compare the impact of each intervention and hence the potential synergistic impact of the MedDiet and PA on fasting concentrations of the following cardiometabolic risk factors: LDL-C, HDL-C, TG, CRP, adiponectin, IL-6, IL-8, TNFA-alpha, SBP, DBP. These comparisons will be performed on two sets of measures at the end of the intervention, i.e. at 16 week (112 days) and 2 days later (16.3 weeks, or 114 days). Secondary objectives also include the comparison of each intervention and hence the potential synergistic impact of the MedDiet and PA on cardiac structure and function and on exercise capacity (VO2max) measured at the end of the 16-week intervention (112 days).

Other pre-specified outcomes include assessment of the associations between changes in study outcomes and in abdominal fat levels as well as exploratory analyses of how the microbiota markers explain the difference between groups in cardiometabolic risk (exploratory objective).

Inclusion Criteria:

• Waist circumference of 80 cm and over for women and 94 cm and over for men
• Serum triglyceride concentration of 1.5 mmol/L or higher
• For pre-menopausal women: regular cycle for at least 3 months, do not become pregnant or breastfeed
• For menopausal women: no hormone or stable dose for at least 6 months

Exclusion Criteria:

• Have a calculated Mediterranean score > 25
• Do > 100 minutes of moderate physical activity per week
• Weight change of > 5 kg in the last 3 months
• Presence of familial hypercholesterolemia, diabetes, history of CVD
• Take medications that affect inflammation and blood lipids
• Have taken anti-diabetic agents in the last 6 months
• Smoker
• Alcohol consumption >14 drinks per week
• Have allergies or aversions to components of the Mediterranean diet
• Follow a structured training program
• Dieting or having a special diet
• Inability to engage in a physical activity program