According to EW:
In the episode, Lady Gaga (playing herself) stops her Gaga Express train in the depressed town of Springfield and tries to boost the spirits of Lisa, who has become a complete social outcast. Using the power of positive thinking and song, can Gaga teach Lisa – and everyone in Springfield — that individuality beats conformity?
The Simpsons has had a long history of including musicians in its illustrious roster of celebrity guests including: George Harrison, Red Hot Chili Peppers, The Ramones, Bette Midler and others.
The Ramones sing Happy Birthday to Mr. Burns
The episode "How I Spent My Summer Vacation," which features Homer's trip to a Rock and Roll fantasy camp guest-starred a plethora of rockers, such as: Elvis Costello, Mick Jagger, Lenny Kravitz, Tom Petty, Keith Richards and Brian Setzer.
Costello, Petty, Richards, Jagger, Kravitz and Setzer cram on the Simpsons couch
Most recently, Green Day made a cameo in The Simpsons movie:
Green Day rocks Springfield
EW adds that Gaga will fittingly wear 18 different outfits in the episode. No word on whether or not any of those are meat-centric.