Disturbances in brain insulin sensitivity are associated not only with obesity and type 2 diabetes, but also with brain aging and cognitive decline. Longitudinal studies suggest that dietary patterns, particularly those high in dairy intake, may impact brain function via the gut-brain axis. Indeed, dairy foods are known to modulate gut microbiota and may, through this pathway, not only improve brain insulin sensitivity and cognitive performance, but also mental health and appetite regulation. However, underlying mechanisms remain largely unexplored. The primary objective of this study is to evaluate, in older adults with overweight or obesity, the effects of a high-dairy food pattern (4-5 daily servings of (butter)milk, cheese, yogurt, or cottage cheese) compared to a low-dairy food pattern (≤1 serving daily) on (regional) brain vascular function and insulin sensitivity. These outcomes will be quantified using the non-invasive MRI perfusion technique Arterial Spin Labeling (ASL), which assesses cerebral blood flow (CBF) in response to intranasal insulin, a validated physiological marker of brain insulin sensitivity. Secondary objectives include changes in cognitive performance (via the CANTAB neuropsychological test battery), gut microbiota composition (via shotgun metagenomic analysis of fecal samples), and appetite-related brain reward activity (via BOLD-fMRI with food cues). Exploratory analyses include conventional cardiometabolic risk markers (blood pressure, lipid and glucose metabolism), and perceivable (consumer) benefits.

Inclusion Criteria:

• Men and postmenopausal women (≥ 2 years since last menstruation);
• Aged between 40-75 years;
• BMI between 25-35 kg/m2 (overweight or obese);
• Low-to-moderate habitual dairy consumption (≤ 3 servings/day);
• Fasting serum total cholesterol < 8.0 mmol/L;
• Fasting serum triacylglycerol < 4.5 mmol/L;
• Fasting plasma glucose < 7.0 mmol/L;
• Systolic blood pressure < 160 mmHg and diastolic blood pressure < 100 mmHg;
• Stable body weight (weight gain or loss < 3 kg in the past three months).

Exclusion Criteria:

• Left-handedness;
• Milk protein allergy or lactose intolerance;
• Current smoker, or smoking cessation < 12 months;
• Familial hypercholesterolemia;
• Abuse of drugs;
• Alcoholic intake >3 standard drinks/day;
• Use of medications, food products or dietary supplements affecting glucose, lipid, or blood pressure regulation, gut microbiota or mental or neurological function, judged by the principal investigator;
• Use of antibiotics within the previous month;
• Use of other biomedical investigational products within the previous month;
• Participation in another clinical trial within the past month;
• Severe medical conditions including type 2 diabetes, epilepsy, asthma, kidney failure, COPD, inflammatory bowel disease, autoimmune diseases, or rheumatoid arthritis;
• History of cardiovascular events (e.g., heart attack, stroke) or active cardiovascular disease;
• Contra-indications for MRI imaging (e.g. pacemaker, metal implants, claustrophobia);
• Willing to donate blood starting from 8 weeks before the study begins, throughout the study, and for 4 weeks after its inclusion;
• Difficult to venipuncture as evidenced during the screening visit.