Discover how long-term exercise rewires fat cells, improves energy metabolism, and fights inflammation for lasting health benefits in adults with obesity.

Study: Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity. Image Credit: Halfpoint / Shutterstock

In a recent study published in the journal Nature Metabolism, researchers in the United States of America investigated the effect of long-term exercise on the abdominal subcutaneous adipose tissue (aSAT) in overweight or obese individuals.

They found that aSAT from exercisers had higher capillary density, fewer macrophages, and greater abundance of proteins linked to angiogenesis, mitochondrial function, ribosomal activity, and lipid storage, potentially contributing to better cardiometabolic health.

The study also identified significant upregulation of oxidative phosphorylation and thermogenesis pathways, indicating enhanced energy metabolism in the aSAT of regular exercisers.

Background

Evidence suggests that in individuals with overweight or obesity, abnormalities in aSAT are linked to insulin resistance and metabolic health issues. These include fibrosis, reduced capillaries, pro-inflammatory macrophage infiltration, and disrupted lipid metabolism, which limits fat storage and increases fatty acid circulation. This can lead to ectopic fat deposits in organs like the liver and muscles, contributing to insulin resistance and inflammation. Improving aSAT by enhancing fat storage, increasing capillarization, reducing fibrosis, and lowering inflammation can benefit metabolic health.

Exercise is recommended to combat obesity-related health problems, but most studies on its effects are confounded by weight loss or short durations. There remains a dearth of research on the long-term effects of endurance exercise on aSAT, independent of weight loss, which is crucial to understanding how exercise can improve cardiometabolic health in those with overweight or obesity. The present study specifically aimed to address these limitations by focusing on endurance exercise without accompanying weight loss, thereby isolating the effects of exercise on aSAT structure and function.

To address this gap, researchers in the present study investigated the effects of regular endurance exercise on the structure, proteomic profile, and remodeling capacity of aSAT in adults with overweight or obesity. They employed comprehensive proteomic and phosphoproteomic analyses to uncover the molecular mechanisms underlying aSAT remodeling, revealing significant alterations in pathways related to angiogenesis, mitochondrial biogenesis, and lipid metabolism.

About the study

The study recruited 52 adults with overweight or obesity (body mass index [BMI]: 25–40 kg/m²) of mean age xx. Based on self-reported activity levels, the participants were categorized into sedentary or non-exercisers (n = 28) and regular exercisers (n = 24). Participants who had been involved in moderate to vigorous intensity aerobic exercise for over 30 minutes at least four days a week for more than two years were classified as exercisers.

For primary comparisons, 16 sedentary individuals (mean age 31 years, 50% male) were pair-matched for sex, adiposity, age, body weight, and BMI with 16 exercisers.

Five exercisers had also engaged in resistance training for over two years. Fresh adipose tissue samples from a subset of 19 exercisers and 24 sedentary individuals were analyzed via exploratory ex vivo experiments.

All the participants maintained stable body weight for at least six months prior to enrollment and had no history of cardiovascular or metabolic diseases.

Body composition was assessed via dual-energy x-ray absorptiometry and bioelectrical impedance analysis, while aerobic fitness was measured using graded exercise tests.

Fasting blood and aSAT samples were used for histological analyses and proteomics and to assess angiogenic capacity and metabolic responses during an oral glucose tolerance test. Statistical analysis involved the Kolmogorov–Smirnov test, log transformation, paired and independent Student’s t-tests, and two-way analysis of variance linear mixed models.

Results and discussion

The exercisers reported nearly tenfold greater physical activity (P = 0.001) and had a peak volume of oxygen (VO₂) uptake approximately 25% higher than the sedentary group (P

Exercisers showed lower insulin resistance indices, such as homeostatic model assessment for insulin resistance (HOMA-IR) and adipose tissue insulin resistance (Adipo-IR). They also showed higher high-density lipoprotein (HDL) cholesterol in exercisers (P

In terms of adipose tissue characteristics, adipocyte size was similar across both the groups, but capillary density and vascular endothelial growth factor α (VEGFα) were greater in exercisers. The study also highlighted a significant upregulation of mitochondrial proteins and ribosomal subunits in aSAT from exercisers, indicating enhanced protein translation capacity and mitochondrial biogenesis. The abundance of Col6a, the collagen type in adipose tissue that is strongly linked to metabolic abnormalities, was also found to be lower in exercisers. Furthermore, adipose tissue macrophage markers were found to be significantly lower in exercisers.

Global proteomics identified 2,536 proteins, revealing 158 differentially expressed proteins, with notable upregulation of ribosomal and mitochondrial proteins in exercisers. Pathway analysis suggested that exercise promotes the activation of the AMPK signaling pathway, which is crucial for mitochondrial biogenesis and lipid metabolism, and enhances thermogenic processes in aSAT.

Targeted immunoblotting corroborated these findings, showing increased levels of ribosomal proteins and oxidative phosphorylation subunits in the exercise group. Ex vivo functional assays demonstrated greater angiogenic capacity and enhanced metabolic activity in explants from exercisers.

Additionally, exercisers showed larger lipid droplets and increased expression of messenger ribonucleic acid (mRNA) of regulatory factors compared to the sedentary group, suggesting enhanced maturation and metabolic activity. The study also reported an upregulation of RNA-binding proteins involved in post-transcriptional regulation, which could play a role in the enhanced adipogenesis observed in exercisers.

The study is limited by its cross-sectional design, reliance on self-reported exercise data, potential selection bias, lack of direct mechanistic links between aSAT changes and metabolic health, and unmatched adiposity in ex vivo experiments.

Conclusion

In conclusion, the study highlights the positive impact of sustained regular exercise on cardiometabolic health and adipose tissue biology in individuals with overweight or obesity, suggesting that exercise promotes beneficial changes in adipose tissue characteristics and associated metabolic functions.

The findings indicate that regular exercise enhances the metabolic activity of aSAT through the upregulation of key pathways such as oxidative phosphorylation and AMPK signaling, contributing to improved lipid storage and energy metabolism.

While short-term exercise may prompt some changes in aSAT, more profound adaptations require longer durations of consistent exercise for improved health outcomes in this population.