The goal of this proposal is to determine the effect of a high protein diet in which the increase in protein intake is derived from different sources (animal vs plant and protein-rich whole foods vs protein isolates) on: i) liver and muscle insulin sensitivity; ii) the metabolic response to a meal, and iii) 24-h plasma concentration profiles of glucose, glucoregulatory hormones, and protein-derived metabolites purported to cause metabolic dysfunction.

Inclusion Criteria:

• age: ≥21 and ≤70 years;
• BMI: >24.5 and <32.5 kg/m2;
• habitual protein intake <0.9 g/kg/day (assessed on 2 weekdays and 2 weekend days by using the HealthWatch 360 app); and
• weight stable (i.e., ≤3% change) and untrained (≤150 min of structured exercise/week) for at least 2 months before entering the study.

Exclusion Criteria:

• prediabetes or type 2 diabetes;
• evidence of chronic kidney disease by medical history or laboratory tests (glomerular filtration rate <60 ml/min/1.73 m2 or an albumin to creatinine ratio in urine ≥30 mg/g);
• vegetarians or vegans;
• intolerance or allergies to ingredients in the metabolic meal or intervention diet;
• take dietary supplements (e.g., pre- and probiotics, fiber, fish oil) or medications known to affect our study outcomes;
• received antibiotic or antifungal treatment (which affect the microbiome and therefore microbial metabolite production) 2 months before entering the study;
• consume tobacco products or excessive alcohol (women: >14 drinks/week; men: >21 drinks/week);
• evidence of significant organ system dysfunction or diseases (e.g., cirrhosis), and
• unwilling or unable to provide informed consent.