Key result
Deletion of IRF2BP2 in human adipocytes and mice increases lipolysis and LIPE expression, leading to adipose tissue inflammation and glucose intolerance.
Why the study?
Although lipolysis is regulated by posttranslational modifications of key enzymes, less is known about the transcriptional mechanisms regulating it.
Does IRF2BP2 deletion affect adipocyte lipolysis and metabolic homeostasis in human adipocytes and mice?
Does IRF2BP2 deletion affect adipocyte lipolysis and metabolic homeostasis in human adipocytes and mice?
IRF2BP2 acts as a transcriptional repressor of adipocyte lipolysis, and its deletion leads to increased free fatty acids, inflammation, and glucose intolerance, highlighting a potential target for metabolic disease.
IRF2BP2 emerges as lipolysis regulator; hypothesis-generating for cardiometabolic therapies, requires in vivo validation.
Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by posttranslational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis. Here, we identify interferon regulatory factor–2 binding protein 2 (IRF2BP2) as a transcriptional repressor of adipocyte lipolysis. Deletion of IRF2BP2 in human adipocytes increases lipolysis without affecting glucose uptake, whereas IRF2BP2 overexpression decreases lipolysis. RNA sequencing, and chromatin immunoprecipitation sequencing analyses show that IRF2BP2 represses lipolysis-related genes, including LIPE , which encodes hormone sensitive lipase, the rate-limiting enzyme in lipolysis. Adipocyte-selective deletion of Irf2bp2 in mice increases Lipe expression and free fatty acid levels, resulting in adipose tissue inflammation and glucose intolerance. Together, these findings demonstrate that IRF2BP2 restrains adipocyte lipolysis and opens avenues to target lipolysis for the treatment of metabolic disease.
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Chen et al. (2025) studied Metabolic disease. Deletion or overexpression of IRF2BP2 vs. Control was evaluated on Adipocyte lipolysis and LIPE expression. Deletion of IRF2BP2 in human adipocytes and mice increases lipolysis and LIPE expression, leading to adipose tissue inflammation and glucose intolerance.
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