It means "Designated Ugly Fat Friend". They don't have to be any of those, but that doesn't mean they don't have friends more attractive than them. The DUFF is basically the least attractive one in the group.
"She's cute, but her friends are hotter. She must be the DUFF."
"He's the youngest in the team and acts as the Gatekeeper to the rest of the team. He's a DUFF."
"That teacher is being left out from other conversations... He's a teacher DUFF."
"He's the youngest in the team and acts as the Gatekeeper to the rest of the team. He's a DUFF."
"That teacher is being left out from other conversations... He's a teacher DUFF."
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