Sodium Homeostasis in Metabolic Syndrome: Sorting out New and Old Players

Symposium — Tuesday, April 25, 2024 — 10:30 AM - 12:30 PM — , Room W196C
Water and Electrolyte Homeostasis Section — Chair: Carolyn Ecelbarger — Co-Chair: Swasti Tiwari

The metabolic syndrome (MetS) constitutes a complex constellation of related disorders associated with excess energy consumption and bodily storage.  Features of MetS include, but are not limited to: dyslipidemia, insulin resistance, visceral adiposity, and hypertension.  Inappropriate renal sodium retention as a result of impaired natriuresis is thought to play a central role in the hypertension associated with MetS.  Nonetheless, mechanisms and key pathways involved are in need of further elucidation.  In this symposium, we provide novel, as well as, updated information relating to sodium homeostasis in this disorder.  We will primarily focus on the renal tubule, its variety of sites of renal reabsorptive action, specific candidate transporters/channels, and those hormonal and paracrine factors that are altered during MetS.  One presentation will provide a comprehensive over-view of sodium reabsorption along the renal tubule and how this has been shown to be altered in MetS.   Other talks will focus more in depth, on the collecting duct and thick ascending limb to highlight precise cellular/molecular changes.  With regard to hormonal influences, we will discuss, in greatest detail, insulin resistance and as a result, elevated circulating insulin levels, which may be at the heart of MetS.  Insulin has been demonstrated to be anti-natriuretic at a number of renal sites and directly influence the activity of a number of sodium reabsorptive pathways along the renal tubule.  One channel which has been fairly extensively studied with regard to insulin actions, is the epithelial sodium channel ENaC.  However, ENaC has also been shown to be activated by the related hormone, insulin-like-growth factor (IGF1), and to add to the complexity, IGF1 and insulin may bind to each others receptors.  The complex relationship between insulin and IGF1 signaling will be detailed.  In addition, to the collecting duct, the MetS may target sodium reabsorption in the thick ascending limb (TAL).  Another talk will highlight this site of the renal tubule.  Novel and well known regulators of the bumetanide-sensitive Na-K-2Cl cotransporter at this site will be discussed, including inflammation, insulin, and nitric oxide (NO).  Finally, direct studies on the effects of insulin on blood pressure have produced mixed results.  One possible reason is that insulin has the capacity to increase nitric oxide in the kidney.  Thus, we will also explore the role of dysregulated nitric oxide (NO) in the sodium retention associated with MetS, discuss insulin-stimulated NO release, as well as highlight novel means by which NO generation is regulated in the kidney, e.g., histone deacetylases.  In sum, this symposium will provide insights into how sodium handling is altered in MetS, identify the roles of new and old players, and hopefully stimulate a lively debate and discussion, as to those factors that are the most important and directly relevant and potential targets in the reduction of hypertension associated with MetS

Speakers

• Regulation of ENaC by Insulin and IGF1: Are They Distinguishable?
  Alexander Staruschenko — , Medical College of Wisconsin


• The renal thick ascending limb and obesity-associated sodium retention: culprit or innocent by-stander?
  Dexter Lee — , Howard University


• Integrative sodium reabsorption along the renal tubule:  global impact of metabolic syndrome
  Carolyn Ecelbarger — , Georgetown University


• Metabolic Syndrome, Insulin, and Renal Sodium Handling
  Vivek Bhalla — Dept. of Medicine/Nephrology, Stanford Univ. Sch. of Med.