The tanks are made for that load, and the tanks are well supported (unlike our Winnebago, which only had one small strap on the black tank... the snap broke... yuk).
We dump and flush them as often as we can, and keep a couple of inches of "slosh" water in them at all times.
The fresh water tank stays full at all times... rather have it and not need it, etc., etc.
The difference in mileage between running with a full tank and an empty tank is so small, as to be insignificant. Weight figures very little in mileage, the real hit to MPG comes from the RPM's needed to push that brick through the air. We drive by the RPM's (about 1,900 to 2,100) to get about 11.2 MPG.
2016 Redhawk 26XD
Me, Dear Wife,
2 Bluetick Hounds
1 Newfoundland / Black Lab Mix
1 Cairn Terrier