Abstract
Lipoprotein lipase (LPL) is the rate limiting enzyme for tissue specific plasma triglyceride (TG) utilization. There is a strong causal link between LPL and cardiovascular health. PURPOSE: Our translational studies investigated the soleus muscle aiming to answer the following questions: What are the mechanisms responsible for the potent process of regulating LPL within the soleus muscle? Can individuals with low fitness levels capitalize on the unique phenotype of the soleus muscle to markedly enhance systemic plasma lipid metabolism through localized contractile activity, even though the muscle constitutes only ~1% of body weight? METHODS: We began by testing the hypothesis that LPL is stimulated by ambulatory activity because of a mechanism involving tissue specific LPL binding to the soleus vasculature, but not in other tissues. 125I-LPL was injected into the left jugular vein to compare relatively inactive vs active rats. Next, we developed a feasible method of isolated plantarflexion in seated humans to determine if targeting the soleus would be sufficient to cause large improvements in lipid metabolism. RESULTS: In rats, there was a strong correlation between endogenous LPL activity and the binding of radiolabeled 125I-LPL (R² = 0.86; P < 0.0001), with activity rapidly increasing binding affinity to the soleus endothelium (~2-fold, P < 0.001), a response absent in less oxidative muscles. In humans, we developed a low-effort seated activity to engage the soleus muscle without causing fatigue or adverse effects, even after prolonged sessions (~5 hours; N = 35). Among 7 participants undergoing invasive tests, this specific activation of soleus lipid metabolism reduced very low-density lipoprotein triglycerides (VLDL-TG) to 73 ± 5% of baseline. CONCLUSION: Sedentary time is increasingly prevalent worldwide, leading to a number of rapidly deleterious effects. Utilizing the fatigue resistant oxidative soleus muscle during seated behaviors provides a potent method of increasing catabolism of VLDL-TG. In addition to providing a method of improving the blood lipid profile, these findings also show that a small muscle can have profound whole-body effects.
Recommended Citation
LeBlanc, Daniel P. and Hamilton, Marc T.
(2025)
"Targeted Soleus Muscle Activation Enhances Very Low-Density Lipoprotein Triglyceride Metabolism via Lipoprotein Lipase,"
International Journal of Exercise Science: Conference Proceedings: Vol. 2:
Iss.
17, Article 23.
Available at:
https://digitalcommons.wku.edu/ijesab/vol2/iss17/23
