Serrano, Nathan

Skeletal muscle is a heterogenous tissue composed of fibers (i.e., cells) with distinct metabolic and contractile properties. Muscle fibers are classified into 2 separate groups: Type 1 fibers which are primarily oxidative, and Type 2 fibers (further subdivided to Types 2a and 2x) which are predominantly glycolytic. Acute exercise induces transcriptional changes in skeletal muscle. However, these changes have been studied at the whole muscle level. The effects of exercise on differential gene expression in distinct muscle fiber types in response to acute exercise remains unclear. In this study, we evaluated gene expression in Type 1, 2a, and 2x muscle fibers in response to acute aerobic exercise. Muscle biopsies were collected from 5 (31±3 yrs) apparently healthy individuals before and 3hrs following an acute 45 min session of cycling exercise performed at 65% of maximal heart rate. Individual muscle fibers (n=138) were isolated from the muscle biopsy sample manually under a microscope. Half of the fiber was used to characterize it as Type 1, 2a, or 2x based on its myosin heavy chain isoform expression content using single fiber SDS-PAGE. The other half of the fiber underwent RNA sequencing. The effects of exercise on fiber types were analyzed using subject specific pseudo-bulk differential expression before and after exercise (Type 1 n=28, 2a n=28, and 2x n=12). Gene counts were normalized as counts per million (CPM) and log2 transformed with a pseudocount of +1. The top 200 differentially expressed genes (DEG’s) were then used to calculate fold changes between fiber types at baseline and in response to exercise. After exercise, 73.5% of DEG’s were upregulated in Type 1 fibers, 52% were upregulated in Type 2a fibers, and 60.5% were downregulated in 2x fibers, relative to baseline. Type 1 fibers showed the greatest increases in gene expression (notably, TPM1 log2FC = 2.46, ATP2A1 log2FC = 3.23, and UQCRB log2FC=0.39) and displayed transcriptional changes consistent with oxidative phosphorylation, calcium signaling, and cytoskeletal remodeling pathways. Type 2a fibers displayed modest increases (ATP2A1 log2FC = 0.34, TNNC2 log2FC = 0.21 and ENO3 log2FC=0.35) and an overall upregulation of glycogenic/gluconeogenesis pathways. Conversely, Type 2x fibers exhibited broad transcriptional suppression and downregulation of calcium signaling pathways. In conclusion, acute aerobic exercise induces gene expression in muscle that is fiber type-specific. Type 1 fibers upregulate genes related to oxidative phosphorylation and calcium signaling, whereas Type 2a fibers upregulate genes related to glycolysis. 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.

Obesity is associated with altered skeletal muscle protein metabolism. While plasma amino acids (AA) stimulate protein synthesis in muscle, it remains unclear how aerobic exercise modifies this response in obesity. In this study, we evaluated basal and amino acid-stimulated skeletal muscle protein fractional synthesis rate (FSR) in humans with obesity, induced by a primed, constant AA infusion (15% Clinisol; 4 mg·kg FFM-1·min-1), immediately after a single bout of acute aerobic exercise. We studied two groups of subjects with obesity: Group 1: AA infusion alone for 240 mins (AA; N = 8; BMI: 34.9 ± 1 kg/m 2 ; body fat percent: 35.2 ± 2) and group 2: acute aerobic exercise followed by AA infusion for 240 mins (AA+EX; N=8; BMI: 36.1 ± 2 kg/m 2 ; body fat percent: 42.4 ± 2). Subjects in the AA+EX group performed 45 minutes of cycling on a stationary bike at 65% VO2 max, and their amino acid infusion started immediately after the exercise ended. A d10-leucine tracer was infused for the entire duration of the study to measure mixed-muscle protein FSR (MMP-FSR). Muscle biopsies from the vastus lateralis were taken at baseline, 45 mins after the start of the amino acid infusion and at the end of the infusion study to determine MMP-FSR. Baseline MMP-FSR values did not differ between groups (p > 0.05). Participants receiving the AA infusion alone exhibited a significant increase in MMP-FSR from baseline to post-infusion (0.060 ± 0.005 to 0.119 ± 0.011 %/hr; p < 0.0001), whereas the AA+EX group showed no significant change from baseline (0.067 ± 0.004 to 0.084 ± 0.009 %/hr; p > 0.05). Plasma insulin concentrations increased significantly in response to the amino acid infusion (p < 0.0001) but did not differ between groups (p > 0.05). Baseline amino acid concentrations were not different between groups (p > 0.05). Among the plasma amino acids (μmol/L) changed, baseline plasma leucine (AA:137 ± 8, AA+EX: 144 ± 10; p > 0.05) increased significantly in both groups during AA infusion but was higher in the AA (424 ± 15) than the AA+EX (226 ± 13) group (p< 0.0001). Similarly, baseline plasma valine (AA: 226 ± 7, AA+EX: 234 ± 19; p > 0.05) increased significantly in both groups during AA infusion but was higher in the AA (553 ± 28) than the AA+EX (456 ± 23) group (p< 0.002). In contrast baseline arginine (AA: 59 ± 5, AA+EX: 71±11; p > 0.05), although it increased significantly in both groups during AA infusion, was lower in the AA (197 ± 3) than the AA+EX (266 ± 11) group (p< 0.0001). Despite marked increases in plasma amino acid and insulin concentrations, the AA+EX group exhibited a blunted muscle protein synthesis response to amino acid stimulation compared with the AA group. In conclusion, aerobic exercise blunts the amino acid-stimulated increase in muscle anabolism in the immediate period after exercise in humans with obesity. This research was supported by the National Institutes of Health/ National Institute of Diabetes and Digestive and Kidney Diseases. 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.

The proportion of the different types of fibers in a given skeletal muscle contributes to its overall metabolic and functional characteristics. Greater proportion of type I muscle fibers is associated with favorable oxidative metabolism and function of the muscle. Humans with obesity have a lower proportion of type I muscle fibers. We discuss how lower proportion of type I fibers in skeletal muscle of humans with obesity may explain metabolic and functional abnormalities reported in these individuals. These include lower muscle glucose disposal rate, mitochondrial content, protein synthesis, and quality/contractile function, as well as increased risk for heart disease, lower levels of physical activity, and propensity for weight gain/resistance to weight loss. We delineate future research directions and the need to examine hybrid muscle fiber populations, which are indicative of a transitory state of fiber phenotype within skeletal muscle. We also describe methodologies for precisely characterizing muscle fibers and gene expression at the single muscle fiber level to enhance our understanding of the regulation of muscle fiber phenotype in obesity. By contextualizing research in the field of muscle fiber type in obesity, we lay a foundation for future advancements and pave the way for translation of this knowledge to address impaired metabolism and function in obesity.