The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy

Figure 2

White adipose tissue (WAT) and inflammation: endocrine-metabolic consequences. A combination of genetic background and endogenous androgen excess could induce WAT mass hypertrophic expansion associated with macrophage infiltration, leading to an abnormal pattern of adipokine secretion. Enhanced WAT-derived leptin release, in turn, impairs tissue sensitivity to insulin (insulin resistance (IR)). Prolonged hyperleptinemia could induce long-form leptin receptor (ObRb) downregulation, namely, at the pancreatic (β- and α-cell) level, thus impairing its negative feedback mechanism on insulin (and glucagon) secretion; moreover, increased release of proinflammatory signals (TNF, IL-1, IL-6, and C-reactive protein (CRP), among others) worsens several functions. In fact, overall WAT dysfunction promotes multiple endocrine-metabolic dysfunctions, such as generalized IR, enhanced reticulum endoplasmic oxidative stress (REOS), enhanced lipolytic activity, cell hypoxia, and apoptosis. These alterations, in turn, affect multiple peripheral organs, namely, liver, muscle, endocrine pancreas, and endothelium functions. FFA: free fatty acid; JUNK: Janus kinase; NF-κB: nuclear factor-κB; HGP: hepatic glucose production; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; DMT2: diabetes mellitus type 2 (adapted from Pagano et al. [108]).