Many factors influence the extent to which exercise promotes weight loss, including exercise intensity, dietary habits, and overall lifestyle. Evidence suggests genetic differences play a role, too. A recent study found that mice with certain variants of PGC1-alpha—a key regulator of metabolism—consume less oxygen and burn less fat during workouts and are more likely to gain weight despite increased activity.

Researchers analyzed gene expression in mice to determine the distribution of the three variants of PGC1-alpha: A, B, and C. Then, they assessed the animals' muscle growth, fat burning, and oxygen consumption during rest, short-term exercise, and long-term exercise. They performed the same assessments on 20 men, half of whom had type 2 diabetes.

They found that although the three variants have similar functions, the A variant is widely distributed throughout the body, but the B and C variants are primarily found in brown adipose tissue, skeletal muscle, and the heart. They found that mice lacking the B and C variants had a diminished response to exercise, consuming less oxygen and burning less fat. These mice gained weight, developed high insulin levels, and were intolerant of cold temperatures. Men who had higher expression of the B and C variants consumed more oxygen and had less body fat, even among those with type 2 diabetes.

These findings suggest that variants of PGC1-alpha influence the body’s response to exercise and highlight potential strategies for treating obesity.

• Read full publication.