Comment on “mineralocorticoid antagonism enhances brown adipose tissue function in humans: A randomized placebo‐controlled cross‐over study”

Control of Adipose Cell Browning and Its Therapeutic Potential

“…In another study, cold exposure produced a translocation in transporter type 4 (GLUT4) and increased glucose uptake in skeletal muscle [247]. Adipose-derived stem cells can be induced to differentiate to beige adipocytes in many ways, and the results of a large amount of research in this area suggest that a substantial number of potential drugs will become available in the next few years [248][249][250][251][252][253][254]. Although many effects remains to be clarified, it is evident that the increase in the activity of beige adipocytes is a consistent mechanism to increase glucose metabolism, supporting its role in treating obesity and related metabolic disorders in humans, especially for type 2 diabetes mellitus [255], which has two key pathophysiological components: peripheral resistance to the action of insulin especially in muscular cells and adipocytes and reduction in insulin secretion in β-pancreatic cells.…”

The novel non‐steroidal MR antagonist finerenone improves metabolic parameters in high‐fat diet‐fed mice and activates brown adipose tissue via AMPK‐ATGL pathway

“…24 Notably, healthy humans treated for two weeks with the MR antagonist spironolactone showed activation of BAT (in response to cold stimuli) at the level of cervical, supraclavicular, axillary, and paravertebral fat depots. 25,26 In clinical practice, the use of spironolactone is limited by side effects such as gynecomastia and erectile dysfunction, since it also binds to androgen and progesterone receptors. [27][28][29] The risk of hyperkalemia also represents a relevant side effect of both steroidal MRAs, spironolactone and eplerenone.…”

“…Indeed, a deeper understanding of the molecular mechanisms regulating BAT function may lead to identify novel molecular targets against adipose tissue (AT) disorders and obesity 24 . Notably, healthy humans treated for two weeks with the MR antagonist spironolactone showed activation of BAT (in response to cold stimuli) at the level of cervical, supraclavicular, axillary, and paravertebral fat depots 25,26 . In clinical practice, the use of spironolactone is limited by side effects such as gynecomastia and erectile dysfunction, since it also binds to androgen and progesterone receptors 27‐29 .…”

Neuroendocrine Control of Energy Metabolism

“…In another study, cold exposure produced a translocation in transporter type 4 (GLUT4) and increased glucose uptake in skeletal muscle [247]. Adipose-derived stem cells can be induced to differentiate to beige adipocytes in many ways, and the results of a large amount of research in this area suggest that a substantial number of potential drugs will become available in the next few years [248][249][250][251][252][253][254]. Although many effects remains to be clarified, it is evident that the increase in the activity of beige adipocytes is a consistent mechanism to increase glucose metabolism, supporting its role in treating obesity and related metabolic disorders in humans, especially for type 2 diabetes mellitus [255], which has two key pathophysiological components: peripheral resistance to the action of insulin especially in muscular cells and adipocytes and reduction in insulin secretion in β-pancreatic cells.…”