Effects of high-fat high-sucrose diet on muscle fiber types in male mice

Obesity has a significant impact on skeletal muscle metabolism and function, leading to reduced insulin sensitivity, muscle atrophy, increased lipid accumulation, and impaired contractile performance. Muscle fiber types play a central role in mediating these effects, given their distinct metabolic and functional properties. In this study, we aimed to assess the impact of obesity induced by a high-fat, high-sucrose diet on muscle fiber type distribution in mice. We studied 17-week-old male C57BL/6 mice divided into two groups: 1) lean controls fed a standard chow diet with regular water, CHOW (n = 5), and 2) mice fed a high-fat/high-sucrose (HFHS) diet (60% fat; n = 5) with sugar-supplemented drinking water (42 g/L; 55% fructose/45% sucrose). Mice were maintained on their respective diets ad libitum for 12 weeks. Gastrocnemius and soleus muscles were collected and analyzed for differences in muscle fiber type distribution by characterizing myosin heavy chain (MHC) isoforms (types 1, 2B, 2X, 2A, and hybrid). Individual muscle fibers were microscopically dissected and analyzed for MHC composition using single-fiber SDS-PAGE methodology. Due to limited resolution between MHC-2X and -2A, these were combined and classified as 2X/A. The average proportion of 2X/A muscle fibers in the gastrocnemius was significantly higher in HFHS mice (43.9% ± 8.7) compared to CHOW controls (6.8% ± 4.4; P = 0.003), indicating a marked shift toward more glycolytic fiber types. In contrast, no difference was observed in the soleus, where 2X/A fiber proportions were similar between HFHS (62.1% ± 5.2) and CHOW (61.9% ± 3.6) mice (P > 0.05). Although not statistically significant, hybrid fiber proportions in the gastrocnemius were lower in HFHS mice (15.4% ± 5.2) than in CHOW mice (22.7% ± 11.5), while the opposite pattern was observed in the soleus, where hybrid fibers were more prevalent in HFHS mice (9.3% ± 3.8) compared to CHOW controls (4.5% ± 2). In conclusion, these findings demonstrate that a HFHS diet shifts muscle fiber composition toward a more glycolytic profile, as indicated by an increase in type 2X/A fibers. This highlights the importance of characterizing muscle fiber adaptations under different dietary conditions to better understand the role of muscle changes in obesity-related metabolic and functional impairments. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.