This study will investigate the effect of body weight, diet, and high blood sugar levels, under controlled feeding conditions, on immune function in individuals with and without obesity.

This study will be a non-randomized, four-arm parallel group, clinical trial under controlled feeding conditions (4-week nutritional intervention using a North American-type diet). A sample size of n=128 participants will be allocated into one of the following groups:

• Individuals without obesity and normoglycemia (NG) (Lean-NG)
• Individuals with obesity and normoglycemia (Obese-NG)
• Individuals with obesity and glucose intolerance (GI) (Obese-GI)
• Individuals with obesity and type 2 diabetes (T2D) (Obese-T2D)

The following outcomes will be analyzed:

• Immune cell function (ex-vivo cytokine production after stimulation with mitogen and T cell proliferation);
• Immune cell phenotypes;
• Systemic inflammation (C-reactive protein and plasma cytokines);
• Glucose, insulin, glycated hemoglobin (HbA1c), and lipids;
• Fatty acids and phospholipds composition in plasma and red blood cells membrane.

Inclusion Criteria

• Age of 18 years to 70 years;
• Body weight stable (± 3%) for at least three months prior to study commencement;
• Body mass index (1) between 18.5 and 24.9 (± 0.5) kg/m2 or (2) between 30 and 50 kg/m2 (± 0.5) kg/m2 or waist circumference >88 cm or > 102 cm for females and males, respectively;

See below for specific group allocation criteria based on glucose, HbA1c, High density lipoprotein cholesterol (HDL-C), and triglycerides.

• Fasting blood glucose levels (mmol/L): < 5.6 (Lean-NG and Obese-NG), 5.6-6.9 (Obese-GI), and ≥ 7.0 (Obese-T2D);
• HbA1c (%): < 5.5 (Lean-NG and Obese-NG), 5.5-6.4 (Obese-GI), and ≥ 6.5 (Obese-T2D);
• Blood Pressure (mmHg): < 130/85 (Lean-NG and Obese-NG), not required for Obese-GI and Obese-T2D;
• Triglycerides (mmol/L): < 1.7 (Lean-NG and Obese-NG), not required for Obese-GI and Obese-T2D;
• HDL-C (mmol/L): ≥ 1.03 for males and ≥ 1.29 for females (Lean-NG and Obese-NG), not required for Obese-GI and Obese-T2D.

Exclusion Criteria

• Current or recent history cardiovascular diseases or events (e.g., ischemic, rheumatic, or congenital heart disease, stroke, peripheral vascular disease, heart failure, familial hypercholesterolemia or other monogenic dyslipidemia), use of cardiac implantable electronic devices;
• Current or recent cancer, including remission, during the last five years;
• Diseases known to affect the immune system, such as infectious, inflammatory, and autoimmune diseases or autoimmune-related or suspected conditions (e.g., T1D, systemic lupus erythematosus, inflammatory bowel disease), except for psoriasis, atopic dermatitis, and rheumatoid arthritis. Continuous use of anti-inflammatory or immunosuppressant drugs and supplements for which washout is not possible, except for medications which participants with obesity could not refrain from (e.g., baby aspirins);
• Renal disorders, endocrine disorders other than T2D (e.g., acromegaly, Addison's disease, Cushing's disease);
• Untreated or uncontrolled thyroid diseases (e.g., Hashimoto's disease, hypothyroidism, hyperthyroidism);
• Known allergy, aversion to any components of the menu, or restricted dietary patterns (e.g., gluten-free diet, vegetarianism, kosher or halal diets) for which accommodations within the menu are not possible;
• Participants under titration of their medication or initiating a new treatment or HbA1c >10.5%;
• Women who are pregnant or plan to become pregnant during the study duration, who are lactating, who have an irregular menstrual cycle or are in perimenopause;
• Regular use of cannabis (e.g. smoking);
• Taking part in any other intervention study that might affect the outcomes of the current study.