| First Author | Kinney CJ | Year | 2021 |
| Journal | Curr Res Physiol | Volume | 4 |
| Pages | 47-59 | PubMed ID | 34746826 |
| Mgi Jnum | J:345932 | Mgi Id | MGI:7612047 |
| Doi | 10.1016/j.crphys.2021.02.003 | Citation | Kinney CJ, et al. (2021) mu-Crystallin in Mouse Skeletal Muscle Promotes a Shift from Glycolytic toward Oxidative Metabolism. Curr Res Physiol 4:47-59 |
| abstractText | mu-Crystallin, encoded by the CRYM gene, binds the thyroid hormones, T(3) and T(4). Because T(3) and T(4) are potent regulators of metabolism and gene expression, and CRYM levels in human skeletal muscle can vary widely, we investigated the effects of overexpression of Crym. We generated transgenic mice, Crym tg, that expressed Crym protein specifically in skeletal muscle at levels 2.6-147.5 fold higher than in controls. Muscular functions, Ca(2+) transients, contractile force, fatigue, running on treadmills or wheels, were not significantly altered, although T(3) levels in tibialis anterior (TA) muscle were elevated ~190-fold and serum T(4) was decreased 1.2-fold. Serum T(3) and thyroid stimulating hormone (TSH) levels were unaffected. Crym transgenic mice studied in metabolic chambers showed a significant decrease in the respiratory exchange ratio (RER) corresponding to a 13.7% increase in fat utilization as an energy source compared to controls. Female but not male Crym tg mice gained weight more rapidly than controls when fed high fat or high simple carbohydrate diets. Although labeling for myosin heavy chains showed no fiber type differences in TA or soleus muscles, application of machine learning algorithms revealed small but significant morphological differences between Crym tg and control soleus fibers. RNA-seq and gene ontology enrichment analysis showed a significant shift towards genes associated with slower muscle function and its metabolic correlate, beta-oxidation. Protein expression showed a similar shift, though with little overlap. Our study shows that mu-crystallin plays an important role in determining substrate utilization in mammalian muscle and that high levels of mu-crystallin are associated with a shift toward greater fat metabolism. |
