Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming

Area of Science:

• Metabolic disease research
• Adipose tissue biology
• Aging and metabolism

Background:

• Beige adipose tissue (BAT) possesses energy-burning capabilities crucial for combating obesity and metabolic disorders.
• Aging diminishes BAT's energy-burning capacity, necessitating an understanding of age-related changes in adipocytes and their precursors.

Approach:

• Investigated the impact of aging on adipocyte stem and progenitor cells (ASPCs) and mature adipocytes during the beiging process.
• Utilized single nucleus RNA-sequencing to analyze adipocyte populations in young and aged mice under varying conditions (cold exposure).
• Examined gene expression profiles, including fibro-inflammatory markers and de novo lipogenesis (DNL) genes, and identified potential regulators like NPR3.

Key Points:

• Aging promotes fibro-inflammatory gene expression in ASPCs, hindering their differentiation into beige adipocytes, although they remain competent in vitro.
• In vivo environmental factors appear to suppress adipogenesis in aged mice.
• Cold exposure induces a specific adipocyte population with high DNL gene expression, a response significantly blunted in aged animals.
• NPR3 identified as a beige fat repressor and an aging-upregulated gene in adipocytes.

Conclusions:

• Aging significantly impedes beige adipogenesis and dysregulates adipocyte responses to cold stimuli.
• The study provides a valuable dataset for exploring age- and cold-associated pathways in adipose tissue.
• Findings highlight potential targets for therapeutic interventions against age-related metabolic dysfunction.