CRBN and AMPK in Metabolic Disorders: Mechanisms and the Impact of Exercise on Systemic Regulation

Cereblon (CRBN) is a multifunctional protein that plays a variety of roles in cellular physiology and is involved in the pathogenesis of numerous diseases. It is established that it functions as a negative modulator of adenosine monophosphate-activated protein kinase (AMPK), which is a principal regulator of energy homeostasis. Recent findings suggest that the interaction between CRBN and AMPK may play a role in both health and disease. The inactivation of AMPK by CRBN has been linked to a range of metabolic disorders, including obesity, diabetes, cardiovascular disease, and non-alcoholic fatty liver disease. Consequently, CRBN represents a novel and attractive target for the treatment of metabolic disorders. Nevertheless, the underlying mechanistic actions of CRBN in the development and amelioration of metabolic disorders remains unclear. Therefore, a fundamental understanding of the relationship between CRBN and AMPK thus offers new insights into potential therapeutic targets for improving and managing metabolic diseases. This review provides an overview of the mechanism of action of CRBN in metabolic disorders and evaluates its benefits on exercise-mediated CRBN responsiveness and AMPK regulation in several tissues and organs.