During mouse embryo development, both muscle progenitor cells (MPCs) and brown adipocytes (BAs) are known to derive from the same Pax7/Myf5 progenitor cells. However, the underlying mechanisms for the cell fate control remain unclear. In Pax7-null MPCs from young mice, several BA-specific genes, including Prdm16 and Ucp1 and many other adipocyte-related genes, were upregulated with a concomitant reduction of Myod and Myf5, two muscle lineage-determining genes. This suggests a cell fate switch from MPC to BA. Consistently, freshly isolated Pax7-null but not wild-type MPCs formed lipid-droplet-containing UCP1 BA in culture. Mechanistically, MyoD and Myf5, both known transcription targets of Pax7 in MPC, potently repress Prdm16, a BA-specific lineage-determining gene, via the E2F4/p107/p130 transcription repressor complex. Importantly, inducible Pax7 ablation in developing mouse embryos promoted brown fat development. Thus, the MyoD/Myf5-E2F4/p107/p130 axis functions in both the Pax7/Myf5 embryonic progenitor cells and postnatal myoblasts to repress the alternative BA fate.
Activation of the thermogenic brown and beige fat is an effective means to increasing whole-body energy expenditure. In this work, a unique label-free method was developed to quantitatively assess the metabolism and thermogenesis of mouse adipose tissues in vivo. Specifically, an optical redox ratio (ORR) based on the endogenous fluorescence of mitochondrial metabolic coenzymes (nicotinamide adenine dinucleotide and flavin adenine dinucleotide) was used to measure the metabolic state of adipocytes. Our findings demonstrate that the ORR provides a label-free and real-time biomarker to determine the thermogenic response of brown, beige and white adipose tissues to a variety of physiological stimulations. In addition, the redox ratio also can be used to evaluate the degree of browning in the white fat of cold-acclimated mice. This technique is important to understand the recruitment and activation of thermogenic adipocytes in mammals and thus can help to develop therapeutic strategies against obesity.
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