Water, Salt, and the Polyol Pathway — AR as a Villain or Protector?

In one earlier post, I briefly mentioned the work of Dr. Rick Johnson regarding the effects of fructose , where he also discussed the impact of high salt concentration and the problems caused by restricted water intake. Both create osmotic stress, which results in activation of the polyol pathway. Let’s explore the mechanism that might reveal some ways to improve the situation—or at least guide us on what to avoid. Let’s first see what happens when the enzyme KHK is knocked out , the enzyme responsible for phosphorylating (activating) fructose. In mice, we saw that eliminating KHK activation (KHK KO) strongly suppresses the effects of both endogenous fructose (produced in the liver from glucose) and dietary fructose . So what happens when water intake is restricted? Does it activate the polyol pathway? Can KHK knockout prevent that? Shutting down fructose metabolism (KHK-KO) has no effect on fructose levels in the hypothalamus during water restriction (WR). Is dietary fructose responsi...