Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology.
In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity.
Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, Rome, Italy Endocrinology Unit Department of Systems Medicine, S. Eugenio and CTO A. Alesini Hospitals, University Tor Vergata, Rome, Italy University San Raffaele Rome, Italy.
Andrea
A
Armani
Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, Rome, Italy Endocrinology Unit Department of Systems Medicine, S. Eugenio and CTO A. Alesini Hospitals, University Tor Vergata, Rome, Italy University San Raffaele Rome, Italy.
Vincenzo
V
Marzolla
Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, Rome, Italy Endocrinology Unit Department of Systems Medicine, S. Eugenio and CTO A. Alesini Hospitals, University Tor Vergata, Rome, Italy University San Raffaele Rome, Italy.
Andrea
A
Fabbri
Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, Rome, Italy Endocrinology Unit Department of Systems Medicine, S. Eugenio and CTO A. Alesini Hospitals, University Tor Vergata, Rome, Italy University San Raffaele Rome, Italy Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, Rome, Italy Endocrinology Unit Department of Systems Medicine, S. Eugenio and CTO A. Alesini Hospitals, University Tor Vergata, Rome, Italy University San Raffaele Rome, Italy massimiliano.caprio@sanraffaele.it.
Massimiliano
M
Caprio
D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000273:Adipose Tissue / Q000503:physiopathology*; D000818:Animals; D001343:Autophagy / Q000502:physiology; D007249:Inflammation / Q000235:genetics; D024821:Metabolic Syndrome / Q000188:drug therapy; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D011499:Protein Processing, Post-Translational; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid
insulin signaling; metabolism; obesity; steroid hormones