Regular endurance exercise led to structural and functional adaptations in abdominal subcutaneous adipose tissue in adults with overweight or obesity—even without weight loss—according to a new study. These adaptations were associated with improved cardiometabolic health markers, with changes observed after sustained exercise over more than 2 years.
The study, published in Nature Metabolism, compared the abdominal subcutaneous adipose tissue (aSAT) characteristics of 16 regular exercisers with those of 16 sedentary adults, matched closely for sex, age, and adiposity.
Key Findings
Researchers found:
- Higher capillary density in aSAT of exercisers (0.20 ± 0.05 vs 0.17 ± 0.04 capillaries per adipocyte, P = .02) than sedentary adults
- Lower collagen VI abundance in exercisers (1.8% ± 0.8% vs 2.3% ± 0.9% stained area, P = .04)
- Fewer pro-inflammatory (CD14+) and anti-inflammatory (CD206+) macrophages in exercisers (39 ± 22 vs 54 ± 34 per mm², P = .06; and 24 ± 14 vs 33 ± 16 per mm², P = .02, respectively)
- Greater abundance of proteins involved in ribosomal function, mitochondrial activity, and lipogenesis in exercisers
- Enhanced angiogenic capacity and lipid storage ability in adipose tissue samples from exercisers in ex vivo experiments.
The study authors emphasized that these adaptations occur in response to long-term endurance exercise, which is required to observe meaningful changes in aSAT. Despite no significant differences in body fat mass, aSAT from exercisers displayed superior structural and proteomic characteristics that may contribute to enhanced cardiometabolic health.
Study Methods
The cross-sectional study recruited 52 adults with overweight or obesity (body mass index [BMI] = 25–40 kg/m²). From this cohort, 16 sedentary participants and 16 exercisers were selected, matched for sex, age, body weight, BMI, and adiposity. Exercisers had engaged in moderate to vigorous aerobic exercise for >30 minutes at least 4 days per week for over 2 years. Participant characteristics included:
- Mean age: 30 ± 5 years (exercisers) vs 31 ± 6 years (sedentary)
- Body fat percentage: 35.2% ± 5.5% (exercisers) vs 35.9% ± 5.5% (sedentary)
- VO2 peak: 54.1 ± 7.0 vs 44.5 ± 4.3 mL/kg FFM/min (P < .001)
- Self-reported physical activity: 57.6 ± 44.8 vs 5.8 ± 6.0 MET-kcal/kg/week (P = .001).
aSAT samples were collected via biopsy. Analyses performed included histological assessment, untargeted global and phosphoproteomics, targeted immunoblots, and ex vivo angiogenesis and 3D spheroid culture assays. Notably, ex vivo experiments revealed that angiogenic capacity was significantly greater in exercisers (7.8% ± 4.1% vs 4.8% ± 3.3% sprout area, P = .01), as was the lipid droplet size in spheroid cultures (284 ± 146 µm² vs 206 ± 91 µm², P = .04), than in sedentary participants. The study highlighted an upregulation of angiogenic, mitochondrial, and lipogenic proteins in exercisers, including a significant increase in capillary density and VEGFα protein abundance (P = .02), indicating enhanced nutrient delivery to adipocytes.
Adipose Tissue Analysis
Additional findings from the adipose tissue analysis included:
- Adipocyte Morphology
- Mean adipocyte size: 3,308 ± 797 µm² (exercisers) vs 2,972 ± 561 µm² (sedentary) (P = .25).
- Extracellular Matrix Components
- Collagen IV and V levels showed no significant differences, but collagen VI (associated with metabolic dysfunction) was notably reduced in exercisers, suggesting potential improvements in tissue functionality.
- MMP-14, an enzyme involved in extracellular matrix remodeling, showed a trend toward higher abundance in exercisers (P = .06), potentially contributing to lower collagen VI levels.
In contrast to local anti-inflammatory changes in aSAT, circulating cytokine levels (eg, IL-6, TNF) did not differ between groups, indicating that exercise-induced changes in adipose tissue may not always correlate with systemic inflammation markers.
Proteomic and Phosphoproteomic Findings
A total of 158 out of 2,536 proteins were differentially expressed between the groups, with upregulated pathways in exercisers including ribosome biogenesis, oxidative phosphorylation, and fatty acid metabolism.
Interestingly, downregulated pathways in exercisers included the complement and coagulation cascades—pathways linked to inflammation.
Phosphoproteomics analysis identified significant enrichment in post-transcriptional modification pathways, including mRNA splicing and RNA polymerase II termination, suggesting enhanced cellular adaptability in exercisers.
Spheroid culture results indicated a significant increase in the expression of SREBF1 (P < .001), a key regulator of lipogenesis, and DGAT1 (P = .06), an enzyme crucial for triglyceride formation, pointing to a potentially greater lipid-storage capacity in exercisers. Notably, collagen I mRNA expression was lower in exercisers (P = .02), further supporting the hypothesis that endurance exercise promotes favorable remodeling of the adipose tissue matrix.
Metabolic Parameters
HOMA-IR—a measure of insulin resistance—was significantly lower in exercisers (1.9 ± 1.7 vs 2.8 ± 1.6, P < .05), as was Adipo-IR (2,364 ± 2,145 vs 3,913 ± 3,143, P = .05).
Additionally, exercisers exhibited higher HDL cholesterol (42.1 ± 13.1 vs 34.7 ± 11.2 mg/dL, P = .05) and adiponectin levels (10,869 ± 4,680 vs 7,017 ± 2,824 ng/mL, P < .05) than sedentary participants.
While insulin sensitivity and lipid profiles were improved in exercisers, fasting glucose levels were similar between groups (4.6 ± 0.8 vs 4.9 ± 0.8 mmol/L, P > .05), and there were no significant differences in fasting fatty acids between groups either.
The study provided detailed evidence of adipose tissue adaptations and systemic metabolic changes associated with regular endurance exercise in adults with overweight or obesity, independent of changes in adiposity.
The authors declared no competing interests.