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Chrna2-driven CRE Is Expressed in Beige Adipocytes
Kezhou Zhu1, Shanshan Liu1, Yunying Huang1,2
1Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract:
Significant research interest has been focused on beige adipocytes, the activation of which improves glucose and lipid homeostasis, therefore representing new therapeutic opportunities for metabolic diseases. Various Cre/Lox-based strategies have been used to investigate the developmental history of beige adipocytes and how these cells adapt to environmental changes. Despite the significant advancement of our understanding of beige adipocyte biology, much of the molecular insights of the beige adipocyte, including its origin and cell type-specific function, remain to be further illustrated. It has previously been shown that Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) has selective functionality in beige adipocytes. In this study, we explore the Chrna2-Cre-driven reporter expression in mouse beige adipocytes in vivo and in vitro. Our findings indicate that Chrna2-Cre expression is present selectively in multiple locular beige adipocytes in subcutaneous inguinal white adipose tissue (iWAT) and differentiated stromal vascular fraction from iWAT. Chrna2-Cre expression was detected in iWAT of young pups and mice after cold exposure where a significant number of beige adipocytes are present. Chrna2-Cre-driven reporter expression is permanent in iWAT postlabeling and can be detected in the iWAT of adult mice or mice that have been housed extensively at thermoneutrality after cold exposure, even though only "inactive dormant" beige adipocytes are present in these mice. Chrna2-Cre expression can also be increased by rosiglitazone treatment and β-adrenergic activation. This research, therefore, introduces the Chrna2-Cre line as a valuable tool for tracking the development of beige adipocytes and investigating beige fat function.
Insights
Researchers developed a Chrna2-Cre mouse model to track beige adipocytes. This tool aids in understanding beige fat development and function, offering insights into metabolic disease therapies.
Area of Science:
- Metabolic disease research
- Adipocyte biology
- Gene expression studies
Background:
- Beige adipocytes are crucial for improving glucose and lipid homeostasis, offering therapeutic potential for metabolic diseases.
- Understanding beige adipocyte origin and function is vital, despite advancements in Cre/Lox strategies.
- Cholinergic receptor nicotinic alpha 2 subunit (Chrna2) shows selective functionality in beige adipocytes.
Purpose of the Study:
- To investigate Chrna2-Cre-driven reporter expression in mouse beige adipocytes.
- To establish Chrna2-Cre as a tool for tracking beige adipocyte development and function.
Main Methods:
- In vivo and in vitro studies of Chrna2-Cre expression in mouse beige adipocytes.
- Analysis of reporter gene expression in subcutaneous inguinal white adipose tissue (iWAT) and stromal vascular fractions.
- Evaluation of Chrna2-Cre expression under various conditions, including cold exposure and drug treatment.
Main Results:
- Chrna2-Cre expression is selectively found in beige adipocytes within iWAT and differentiated stromal vascular fractions.
- Expression is detected in young pups and post-cold exposure, correlating with beige adipocyte presence.
- Reporter expression is permanent in iWAT, detectable even in dormant beige adipocytes after environmental manipulation.
- Chrna2-Cre expression increases with rosiglitazone treatment and beta-adrenergic activation.
Conclusions:
- The Chrna2-Cre mouse line is a valuable tool for studying beige adipocyte development.
- This model facilitates research into beige fat function and its role in metabolic health.
- Findings support the use of Chrna2-Cre for investigating therapeutic strategies for metabolic disorders.
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