The AdipoChaser mouse: A model tracking adipogenesis in vivo

Area of Science:

• Metabolic science
• Adipose tissue biology
• Developmental biology

Background:

• White adipose tissue (WAT) exhibits plasticity, but its depot-specific dynamics and adipocyte turnover remain poorly understood due to technical limitations.
• Abnormal WAT expansion contributes to obesity and metabolic disorders, highlighting the need for precise studies on adipocyte life cycles.
• Previous methods for assessing adipocyte turnover were indirect, limiting insights into adipose tissue dynamics under physiological challenges.

Purpose of the Study:

• To investigate the life cycle and turnover rates of adipocytes in different white adipose depots using a novel inducible labeling system.
• To elucidate the developmental timing of adipocyte differentiation in various fat depots.
• To examine how physiological challenges like high-fat diet, cold exposure, and adrenergic stimulation affect adipogenesis and adipocyte dynamics.

Main Methods:

• Development and utilization of the "AdipoChaser" mouse model for inducible and permanent labeling of mature adipocytes.
• Analysis of adipocyte dynamics in response to high-fat diet, cold exposure, and beta-3 adrenergic agonist stimulation.
• Comparative assessment of adipogenesis and hypertrophy in epididymal and subcutaneous fat depots.

Main Results:

• Epididymal fat depots exhibit significant adipogenesis after high-fat feeding, while subcutaneous depots primarily undergo hypertrophy with low adipogenesis.
• Beige adipocytes in subcutaneous fat depots largely originate from de novo adipogenesis during cold or beta-3 agonist-induced browning.
• Cold exposure and beta-3 agonist stimulation promote substantial white adipogenesis in the epididymal fat depot.
• Adipocytes in gonadal fat depots differentiate postnatally, whereas subcutaneous adipocytes differentiate during embryonic development (days 14-18).

Conclusions:

• The AdipoChaser mouse model provides unprecedented insights into white adipose tissue dynamics and adipocyte turnover.
• Adipose depot-specific differences in adipogenesis and developmental timing are critical for understanding obesity and metabolic health.
• Adipose tissue plasticity is significantly influenced by physiological challenges, with distinct depot responses impacting overall metabolic regulation.