Transdifferentiating Muscle Stem Cells into Brown Fat to Treat Metabolic Disorders

Abstract

Metabolic disorders, such as obesity and diabetes, pose increasing global health challenges with limited long-term success from existing treatments, leading to high worldwide morbidity and mortality. Our project explored a novel approach to treat obesity by transdifferentiating muscle stem cells (MuSCs) into brown adipose tissue (BAT), which expends energy as heat, in contrast to white adipose tissue which stores energy as fat. The objective was to identify a specific MuSC subpopulation with an enhanced capacity to develop into BAT. The methods involved isolating MuSCs from mouse hindlimb muscles, sorting them into subpopulations based on Sca1 expression levels with fluorescence-activated cell sorting (FACS), and growing them in a pro-adipogenic medium to induce brown adipocyte differentiation. We analyzed the efficiency of BAT transdifferentiation through morphological changes, immunostaining for brown adipocyte markers, and quantification of lipid droplets. Preliminary analysis from the first two experiments revealed no significant expression of BAT derived from MuSC in either the Sca1- or Sca1+ subpopulations, suggesting the need to modify the methods of future experiments to obtain more meaningful results.