Abstract
A growing body of research indicates that cortisol, the glucocorticoid product of the activation of the hypothalamic-pituitary-adrenal axis, plays a role in the pathophysiology of metabolic syndrome. In this regard, chronic exposure to cortisol is associated with risk factors related to metabolic syndrome like weight gain, type 2 diabetes, hypertension, among others. Mifepristone is the only FDA-approved drug with antiglucocorticoids properties for improved the glycemic control in patients with type 2 patients secondary to endogenous Cushing’s syndrome. Mifepristone also have been shown positive effects in rodents models of diabetes and patients with obesity due to antipsychotic treatment. However, the underlying molecular mechanisms are not fully understood. In this perspective, we summarized the literature regarding the beneficial effects of mifepristone in metabolic syndrome from animal studies to clinical research. Also, we propose a potential mechanism for the beneficial effects in insulin sensitivity which involved the regulation of mitochondrial function in muscle cells.
Highlights
Mifepristone, known as RU486, was the result of the biomedical revolution forced by the wave of womens movements in the 20th century seeking to control their reproductive life (Spitz, 2010)
Little is known about the mechanisms involved in the hypoglycemic effects of mifepristone. In this perspective article, we briefly summarize the available evidence on the beneficial effects of mifepristone in Cushing’s syndrome and metabolic syndrome and, propose a feasible mode of action that involves the regulation of mitochondrial function, which could explain mifepristone insulin-sensitizing effects
Our results show that mifepristone induces a non-statistical increase in Dynamin-related protein 1 (DRP1) without changes in MFN2 protein levels, which could be associate with an increase in mitochondrial fragmentation (Figure 1B) (Sebastián et al, 2017)
Summary
Mifepristone, known as RU486, was the result of the biomedical revolution forced by the wave of womens movements in the 20th century seeking to control their reproductive life (Spitz, 2010). Cushing’s syndrome (CS) is a condition where cortisol plasma levels are high for a long period of time, developing different signs and symptoms, such as weight gain (especially in the upper body), rounded face, insulin resistance, hypertension, osteoporosis and/or muscle weakness (Newell-Price et al, 2006).
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