Emerging evidence has linked circadian clock genes to glucose homeostasis and exercise. Skeletal muscle-specific BMAL1, as one of the circadian clock activators, is crucial in maintaining glucose homeostasis in mouse models of metabolic disease. In humans, exercise may enhance circulating BMAL1. However,the role of skeletal muscle BMAL1 along with other clock genes on human glucose metabolism are unknown.Herein, we evaluated whether a lifestyle intervention alters expression of skeletal muscle circadian clock genes in adults with obesity and whether the changes were related to systemic improvements.


Eighteen adults (Age: 66±4.5; BMI: 34±3.4) participated in 12 weeks of exercise plus eucaloric diet.Pre/post assessments included body composition (DXA), insulin sensitivity (euglycemic-hyperinsulinemic clamp), and vastus lateralis muscle biopsies (fasted state, ~8:00 AM). Real-time PCR was used to assess skeletal muscle Bmal1, Clock, CRY1/2, PER 1/2, and MyoD1 gene expression. Significant gene targets were further confirmed at the protein level by Western blot in a subset of 6 participants.


Body composition (BMI, DXA) and insulin sensitivity improved (P > 0.05). Bmal1 gene (fold change: 1.65±1.04; P=0.045) and protein (fold change: 1.19±0.05; P=0.01) expression increased. MyoD1 gene expression decreased (fold change: 0.71±0.26; P=0.01), while protein was not different.Other clock genes were unchanged.BMAL1 gene fold change correlated with delta BMI (r=-0.52, P=0.046).Correlation between BMAL1 protein fold change and baseline GDR was trending (r=0.82; P=0.053).


Skeletal muscle-specific BMAL1 is increased after a 12-wk lifestyle intervention in adults with obesity, accompanied by improvements in body composition and skeletal muscle insulin sensitivity. These data provide preliminary evidence that exercise induced skeletal muscle BMAL1 may play a role in improving glucose homeostasis in adults with obesity.