Exercise and Diet Responses in Adult Men With Obesity by MC4R Genotype and Metabolic Health

This was a completed, single-center lifestyle intervention study involving adult men with obesity in Harbin, China.

Eligible participants were men aged 18 to 59 years with a body mass index of at least 28 kg/m2 and a waist circumference of at least 90 cm. At baseline, participants were classified as having metabolically healthy obesity or metabolically unhealthy obesity using criteria based on the National Cholesterol Education Program Adult Treatment Panel III.

Metabolically unhealthy obesity was defined as obesity accompanied by at least two of the following metabolic abnormalities: elevated blood pressure, elevated fasting blood glucose, elevated triglycerides, or reduced high-density lipoprotein cholesterol. Metabolically healthy obesity was defined as obesity accompanied by no more than one of these abnormalities.

All participants received the same 12-week supervised exercise and dietary intervention. The exercise program was conducted 5 days per week and consisted of aerobic exercise performed at approximately 60% to 70% of maximum heart rate and resistance exercise performed at approximately 40% to 60% of one-repetition maximum.

Daily energy intake was individualized according to standard body weight. The planned macronutrient distribution was approximately 50% to 60% of energy from carbohydrates, 15% to 20% from protein, and 20% to 30% from fat.

Anthropometric and body-composition assessments included body weight, body mass index, fat mass, body fat percentage, muscle mass, waist circumference, hip circumference, and waist-to-hip ratio. Physical fitness assessments included vital capacity, handgrip strength, vertical jump, push-ups, sit-ups, sit-and-reach flexibility, one-leg standing with eyes closed, choice reaction time, and back strength.

Physiological and biochemical assessments included resting heart rate, systolic and diastolic blood pressure, fasting blood glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, and fasting insulin. Measurements were conducted at baseline and after 12 weeks.

MC4R rs17782313 genotype and baseline metabolic phenotype were analytical stratification variables. They were not used to assign different interventions. The study evaluated changes from baseline to week 12 and examined whether intervention responses were associated with metabolic phenotype, MC4R genotype, or their interaction.

Inclusion criteria

• Male sex
• Age 18 to 59 years
• Body mass index of at least 28 kg/m2
• Waist circumference of at least 90 cm
• Able and willing to provide written informed consent
• Able and willing to participate in the 12-week supervised exercise and dietary intervention and complete the scheduled assessments

Exclusion criteria

• Severe hepatic insufficiency
• Severe renal insufficiency
• Cardiovascular disease
• Other clinically significant vascular disease
• Current use of glucose-lowering medication
• Current use of antihypertensive medication
• Current use of lipid-lowering medication
• Unable or unwilling to comply with the intervention and assessment schedule