Pyruvate Kinase M2: a novel regulator of adipogenesis

Obesity is the cornerstone of many other conditions, with far-reaching impacts on numerous body systems and quality of life. Obesity is closely and likely causally associated with metabolic syndrome and consequent atherosclerosis, heart disease, stroke, and type 2 diabetes as well as diseases such as cancer and osteoarthritis. Recent studies suggest exploring the possibility of activating brown adipose tissue as a potential anti-obesity strategy. However, understanding the mechanisms underlying the processes of brown adipogenesis and browning is foundational for effectively promoting this strategy as a primary, secondary, and/ or tertiary preventive measure against obesity. Additionally, recent studies have identified the glycolytic enzyme pyruvate kinase M2 (PKM2), as a novel regulator of white and brown adipogenesis. Yet, the molecular mechanisms remain to be elucidated. In the current study, we investigated the effects of PKM2 deficiency on white and brown fat adipogenesis using shRNA-mediated lentiviral approach. We also investigated the underlying molecular mechanisms. Preliminary findings demonstrate that deletion of PKM2 enhances brown fat adipogenesis via modulation of the β-catenin signaling pathway. Additionally, disruption of β-catenin activity altered adipocytes differentiation and mimicked the effects of PKM2 deficiency on adipogenesis. Taken together, our study suggests that targeting PKM2/β-catenin axis may serve as a strategy to promote brown fat adipogenesis, enhance whole body energy expenditure, and prevent obesity and its associated complications.