if the \newcommand definition occurs in the same note before its usage then it should work even after reloading Obsidian, at least it does for me.
across different notes or if used before its definition, the command is not registered at first. closing the note and reopening should be sufficient.
the way i deal with these issues is to use the Extended MathJax community plugin which lets the user define commands in a separate file that get registered upon Obsidian.