Physiological Changes in Response to Skeletal Muscle Specific High Expression of mu‐Crystallin Following High and Low‐Fat Diets

Abstract

Approximately 20 percent of the population expresses high levels of the thyroid hormone binding protein mu‐crystallin in skeletal muscle while the rest of the population expresses little to no mu‐crystallin. Since the thyroid hormones, T3 and T4, are potent regulators of metabolism and thermogenic regulation, our studies focus on the consequences of skeletal‐specific high expression (SM‐HE) of mu‐crystallin. We hypothesize that SM‐HE of mu‐crystallin influences cellular and metabolic changes in a diet‐ and sex‐ specific manner by influencing changes in gene expression.To evaluate this, we generated transgenic mice (Crym‐tg) that over‐express mu‐crystallin in skeletal muscle, equivalent to human high expressors, which resulted in high levels of accumulation of T3 in muscle tissue. Respiratory exchange ratio (RER) in these mice indicated a small but significant increase in utilization of fat as an energy source.In high‐ and low‐fat diet studies, we found differences between Crym‐tg and controls as well as sex specific differences. Following a 16‐week exposure, Crym‐tg males on high‐fat diet and Crym‐tg females on low‐fat diet weighed more than controls whereas Crym‐tg males on low‐fat diet and Crym‐tg females on high‐fat diet weighed less than controls. These differences were consistent with the results of glucose tolerance tests, in which only the Crym‐tg mice that weighed more than controls showed a significant increase in sensitivity to glucose. We are currently evaluating these results to understand their basis in transcriptomic and proteomic data, which have already revealed increased expression of genes involved in fatty acid oxidation and decreased expression of genes involved in glycolytic metabolism (Kinney et al. (2021) Curr Res Physiol. 4:47‐59.) as well as some members of the insulin signaling pathway.