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"What's up?" isn't really an inquiry about how you are; it means "what's new?" or "what's going on?" It can be used just as a greeting, without expecting an answer to the question.
For "what's up?" I would use it as a very casual greeting: "Hey, what's up?" "Not much, you?" It is similar to "how are you" as a checking-in sort of pleasantry, but it doesn't mean "how are you."
gutoEE escreveu:Lembrando que a resposta mais comum é "not much",
No sentido de "nenhuma novidade".