In colloquial English, we have an idiomatic greeting “What’s up?” (a contraction for “What is up?”) meaning, “How are you?” Similar to “Wie gehts?”
It’s sometimes expanded to “What’s up with you?” (adding the ‘with you’ intensifies the question with the connotation that something is wrong and the questioner definitely wants an answer – not just a rhetorical greeting anymore). Similarly, there’s “What’s up with that?” to ask about something that’s wrong or troubling
In urban/street/ghetto/Black/rap usage, verbs tend to loose what little inflection in English that they have. And so, the phrase becomes, “What up?” or "What up widchyu? (a slurring of ‘with you’), or “What up widdat?” [a slurring of ‘with that’])
“Word” has been adequately covered. Though, I’ll add that I believe it’s origin lies in Black gospel churches where ‘the Word of the Lord is true’, leading to the faithful one speaking a true ‘word.’ And thus, ‘word’ --> ‘true’ —> general acknowledgment of agreement —> OK.
In the U.S., we have the situation where the majority White culture picks up slang from the Black/rap culture. This is in itself humorous and ironic on many levels.
In Futurama, they often make the in-joke that words and styles we may consider to be wrong or just a fad actually become mainstream in the future.
And so, we have Frye, who greets an alien with his 20th century street slang, and the alien, surprisingly, replies in kind. In other words, this Black/rap slang becomes standard English throughout the universe.
{For a similar joke, consider that they tell Frye that in the 30th century, the correct pronunciation of ‘ask’ is ‘aks,’ which is a somewhat common mispronunciation in the 20th century. Ever since that episode, all the 30th century characters pronounced ‘ask’ as ‘aks.’}
Peace.