Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function

Area of Science:

• Metabolism and Endocrinology
• Cell Biology
• Genetics

Background:

• Cold exposure induces beige adipocyte formation, enhancing energy expenditure and glucose metabolism.
• Therapeutic applications of beige adipocytes are limited by a lack of tools to study their development and function.
• Identifying the progenitor cells responsible for beige adipocyte formation is crucial for understanding 'beiging'.

Purpose of the Study:

• To identify and characterize the progenitor cells that give rise to cold-induced beige adipocytes.
• To evaluate genetic tools for tracking and manipulating beige adipocyte development.
• To assess the functional role of identified progenitors in thermogenesis and glucose homeostasis.

Main Methods:

• Screening of 12 Cre/inducible Cre mouse strains to mark adipocyte, muscle, and mural lineages.
• Utilizing SMA-Cre(ERT2) and SMA-rtTA mouse models for lineage tracing of beige adipocyte progenitors.
• Assessing the impact of disrupting SMA-tracked progenitor function on thermoregulation and blood glucose levels.

Main Results:

• Perivascular mural cells, marked by SMA-based strains, were identified as the primary progenitors of cold-induced beige adipocytes.
• SMA-marked progenitors were essential for the 'beiging' process and contributed to the majority of cold-induced beige adipocytes.
• Disruption of SMA-tracked progenitor function led to impaired thermoregulation and hyperglycemia.

Conclusions:

• SMA-engineered mouse models are valuable tools for tracking and manipulating beige adipocyte progenitors.
• Perivascular mural cells play a critical role in beige adipocyte formation and function.
• Understanding beige adipocyte development is key for potential therapeutic strategies targeting metabolic disorders.