If you let your car sit for a month, the battery may drain and the car might not start. They were designed in part around the assumption of regular use.

So too has evolution - through the happenstance and accidents of natural selection - ended up relying on the movement and use of the human body to regulate hormones, neurotransmitters, and who all knows what else. Exercise can help release endorphins, dopamine, norepinephrine, serotonin...

Unsuprisingly, when we muck with that, there are problems. Not needing to move to avoid danger or to collect nutrition for basic survival is an extremely recent thing on evolutionary timescales, so this wasn't a problem before.