You're pretty limited as far as reducing weight. You can't go camping with your water tank empty or without the fridge stocked with food.
I don't think there is a lot you can do as far as wind resistance, but some folks claim
THESE things help some. One thing to keep in mind though, slowing down even just as little as 5 mph, can make a big difference in the MPG when pulling a trailer.
One other thing, make sure your tires are all properly inflated. A underinflated tire increases rolling resistance as well as sway in cross winds. With a heavily loaded truck/trailer, underinflated tires are vulnerable to overheating and subsequent blow-outs.
FWIW, I usually run my trailer tires within just a few psi of the max pressure as stated on the side of the tire.