This is an exploratory controlled before-after study, which involves 112 participants, of whom 28 are with normal weight and 84 are overweight or obese. Twelve weeks of caloric-restriction dietary intervention will be conducted in the overweight or obese participants. Before and after the 12-week intervention, metabolic health will be characterized by metabolic homeostasis, determined via comprehensive measurements of dynamic postprandial metabolic responses to a standardized mixed macronutrient tolerance test (75 g glucose, 60 g fat, 20 g protein) in a whole-room indirect calorimeter. The objectives of this study are

1. to characterize dynamic metabolic response elicited by acute nutritional and acute exercise challenges,
2. to elucidate biological mechanisms underlying inter-individual heterogeneity in these responses,
3. to predict prospective weight loss over the intervention using heterogeneous metabolic responses to acute challenges

The objectives of this study are 1) to characterize dynamic metabolic response elicited by acute nutritional and acute exercise challenges, 2) to elucidate biological mechanisms underlying inter-individual heterogeneity in these responses, and 3) to predict prospective weight loss over the intervention using heterogeneous metabolic responses to acute challenges.

In this study, 84 overweight or obese participants (BMI ≥ 24 kg/m2) and 28 normal weight participants (18.5 ≤ BMI<24 kg/m2) will be recruited and receive 12-week caloric-restriction dietary or weight maintenance interventions. Before and after the 12-week interventions, metabolic homeostasis will be used to characterize metabolic health and to be determined using comprehensive measurements of dynamic changes in postprandial metabolic responses (including energy metabolism, multiple clinical biomarkers, metabolomic signatures, gut microbiota, genetic signatures etc.) after standardized mixed macronutrient tolerance test (75 g glucose, 60 g fat and 20 g protein) in whole room indirect calorimeter under both resting and exercise conditions. In addition, data from dietary intake, anthropometric measurements, body composition, psychosocial measures, behavior questionnaires and 14-day continuous glucose monitoring will also be collected to characterize metabolic homeostasis. During the interventions, participants will receive personalized dietary advice, behavior guidance and nutritional and lifestyle education by dietitian and physicians. APP-connected wearable devices will be utilized to monitor their dietary intakes, physical activities and sleep conditions, and an application-connected scale will be used to monitor their weight changes during interventions. The study's protocol has been approved by the Ethics Committee of Sir Run Run Shaw Hospital.

Inclusion Criteria:

• 20-70 years of age, inclusive
• BMI ≥ 24kg/m2
• Not in other clinical studies currently or in the past three months

Exclusion Criteria:

• Fasting glucose >7.0mmol/L or diagnosed diabetes or taking insulin or other blood glucose-lowering drugs
• Blood pressure > 160/100 mmHg; diagnosed phase II or III hypertension or cannot decrease SBP under 160mmHg after anti-hypertension drugs
• Fasting blood TG≥ 5.7 mmol/L or fasting LDL-C≥ 4.9 mmol/L or cannot control TG < 5.7 mmol/L or LDL-C < 4.9 mmol/L after taking lipid lowering drugs
• Pregnant or lactating
• Attempting to change body weight in the past 3 months
• Use of antibiotic in the preceding 3 months for 3-serial days
• Use of estrogen therapy or hormonal drugs in the preceding 6 months
• Smokers
• History of alcohol abuse or other substance abuse (Alcohol abuse is defined as regular alcohol consumption > 40 g/day for females or > 80 g/day for males)
• Severe renal disease or liver disease
• Severe gastrointestinal diseases
• Surgical events preceding 1 year (except appendicitis or hernia surgery)
• Severe cardiovascular or cerebrovascular diseases
• Implantation of heart stent or any device containing metal material
• Cancer or receiving radiotherapy and chemotherapy within 5 years
• Hyperthyroidism or hypothyroidism
• Suffering from AIDS, hepatitis A, hepatitis B and other infectious diseases
• Claustrophobia
• Physical disability
• Any mental disorders or current use of antidepressants
• Cognitive disability