Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming

Area of Science:

• Metabolic disease research
• Adipose tissue biology
• Aging research

Background:

• Beige adipose tissue possesses energy-burning capabilities beneficial for combating obesity and metabolic disorders.
• Aging diminishes the efficacy of beige adipose tissue, posing a challenge for metabolic health.
• Understanding how aging affects beige adipocyte development and function is crucial for therapeutic interventions.

Purpose of the Study:

• To investigate the impact of aging on adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice.
• To identify molecular mechanisms underlying age-related decline in beige adipogenesis and cold-induced thermogenesis.
• To explore the role of fibro-inflammatory genes and specific markers like Npr3 in aging adipose tissue.

Main Methods:

• Comparative analysis of ASPCs and adipocytes from young and aged mice.
• In vitro differentiation assays for beige adipogenesis.
• Single nucleus RNA-sequencing of adipocytes.
• Gene expression analysis, including Cd9 and Npr3.

Main Results:

• Aging increases fibro-inflammatory gene expression in ASPCs, inhibiting their differentiation into beige adipocytes.
• In vitro studies show aged ASPCs retain beige differentiation potential, suggesting in vivo environmental suppression.
• Aging blunts cold-induced de novo lipogenesis (DNL) in adipocytes and alters adipocyte population composition.
• Npr3 identified as a marker for a white adipocyte subset and upregulated with aging.

Conclusions:

• Aging significantly impairs beige adipogenesis and dysregulates adipocyte responses to cold exposure in mice.
• Environmental factors, rather than intrinsic ASPC defects, appear to suppress in vivo beige adipogenesis with aging.
• The study provides a valuable resource for identifying aging- and cold-regulated pathways in adipose tissue for future therapeutic development.