INTRODUCTION:
Skeletal muscle is the largest metabolic organ in the human body, and its mitochondrial function is crucial for lipid metabolism. Current domestic and international research mainly classifies skeletal muscle mitochondria into subsarcolemmal mitochondria (SSM) and intermyofibrillar mitochondria (IFM), but their specific roles in energy metabolism remain debated. This study investigated SSM and IFM mitochondrial function and energy metabolism changes under aerobic exercise and intermittent fasting in high-fat diet-induced obese rats.
METHODS:
SD rats were divided into normal diet and high-fat/high-fructose/high-cholesterol (HFHC) diet groups. After 12 weeks, the normal group was randomized into control (C) and exercise (E) subgroups; the HFHC group was randomized into high-fat control (HC), high-fat exercise (HE), and high-fat fasting (HF) subgroups. Interventions lasted 8 weeks (n=10/group). Oil Red O staining observed lipid accumulation (n=4); fresh quadriceps femoris was used to isolate SSM and IFM (n=6). Mitochondrial membrane potential (JC-1 ratio), oxidative stress (ROS), respiratory function (RCR=State III/State IV), and fatty acid oxidation (FAO) were measured using corresponding kits (Beyotime C2006, S0034S; MitoXpress MX-200-4).
RESULTS:
1) Compared with group C, HC showed significantly increased lipid droplet area (16.45±4.82% vs 61.87±11.65%, p<0.05); decreased SSM and IFM JC-1 ratios (5.188±2.928 vs 3.143±1.994, 6.601±2.652 vs 4.355±2.536, p<0.05); increased SSM and IFM ROS (10798±9701 vs 17855±7147, 4496±1519 vs 8932±2669, p<0.05); and reduced SSM FAO (23290±1083 vs 19150±1412 RFU/min, p<0.05).
2) Compared with HC, HE showed significantly increased SSM and IFM JC-1 ratios (5.410±2.675, 7.829±3.552, p<0.05); decreased SSM ROS (5506±1760, p<0.05); elevated SSM and IFM RCR (10.36±2.357, 10.72±1.721, p<0.05); and increased SSM FAO (27130±1762 RFU/min, p<0.05).
3) Compared with HC, HF showed significantly increased SSM and IFM JC-1 ratios (5.410±2.675, 7.829±3.552, p<0.05); higher IFM ROS than HC (9579±8236, p>0.05); elevated SSM and IFM RCR (10.87±3.467, 11.25±4.179, p<0.05); and increased SSM FAO (25610±1693 RFU/min, p<0.05).
CONCLUSION:
1) High-fat diet-induced obesity causes skeletal muscle lipid deposition, reduced SSM/IFM membrane potential, increased oxidative stress, decreased FAO, and impaired mitochondrial function.
2) Aerobic exercise improves SSM/IFM membrane potential and RCR, reduces SSM oxidative stress, enhances SSM FAO, and repairs mitochondrial energy metabolism.
3) Intermittent fasting improves SSM/IFM membrane potential and RCR, enhances SSM FAO, but has no effect on IFM oxidative stress; its regulatory mechanism differs from aerobic exercise, and SSM/IFM action mechanisms need further study.