When multiple gay men connect each other mouth to dick. The act of twisting their bodies in order to position themselves correctly is what causes The Twizzler effect.
A popular TV show in the 80's about Capatin Kizzle, his sidekick Spizzle, and their travels through the galaxy on the Starship Enterprizzle, ridding the world of Borgizzles and Kilingizzles.
"That is off the hook for real" would be the literal meaning of the phrase. It means that something is extremely novel and interesting, and that you're dumb enough to think you sound cool adding "izzle" to the end of your words.
Dude A: Hey dude, have you seen Frank's new car?
Dude B: Why yes I have. That tizzle off the hizzlefoshizzle.
Dude A: WTF?!?!?!