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Charlize Theron and Seth MacFarlane star in "A Million Ways To Die In The West", out in the UAE on May 29, 2014.

The day after the premiere of their new comedy, A Million Ways to Die in the West — and an after-party that rolled on until 4am — Seth MacFarlane and Charlize Theron were each recovering in their own ways. He slept in and ate a grilled meat and cheese sandwich; she went to yoga and sipped green tea.

“I feel like such a loser,” Theron said, joining MacFarlane in the bar of a Beverly Hills hotel. “If I can go to yoga, I did not do it right.”

“No, you did it right,” MacFarlane said, clutching his head. Theron stared at her obviously suffering director and co-star and laughed so loudly the sound reverberated through the bar and carried over a pianist playing Tiny Dancer.

MacFarlane and Theron have an easy rapport, which they deploy with gusto in A Million Ways to Die in the West. In the raunchy, R-rated western comedy their outsider characters discover a shared hatred of life on the frontier, with all of its violence and discomfort.

“At the core of this movie’s premise is that if you’re not an alpha male, what can you do out there?” said MacFarlane, who also wrote the film, with Alec Sulkin and Wellesley Wild. “You’ve just gotta keep your head down.”

Both MacFarlane and Theron are venturing into new territory with A Million Ways to Die in the West, along with Universal Pictures, which is releasing the film in the UAE on Thursday. MacFarlane, 40, who directed the R-rated hit Ted, created the animated sitcom Family Guy and somewhat controversially hosted the Oscars in 2013, delivers his first starring film role, as Albert, a sheep farmer ill-suited to life in 1882 Arizona.

Just a movie with the word “West” in the title is a gamble — recent westerns including last year’s Lone Ranger update and 2011’s Cowboys & Aliens flopped at the box office. And a western comedy starring an untested leading man is even more of an oddity — the most successful films in the niche genre, such as 1974’s Blazing Saddles and 1986’s Three Amigos, starred actors who were already well established at the box office.

Theron, 38, an Oscar winner who built her career on the strength of dramatic performances in movies such as Monster and North Country, is taking her first dip into a straight-up comedy as Anna, the dissatisfied wife of a notorious outlaw (Liam Neeson) who blows into town just as Albert is smarting over a break-up. Anna teaches Albert to shoot and to stand up for himself, helping him recover after his girlfriend, Louise (Amanda Seyfried), leaves him for a smarmy groomer of mustaches (Neil Patrick Harris).

Both MacFarlane and Theron like westerns for different reasons. For a guy who built his career on satire, MacFarlane has a surprising affection for sincere characters like Gunsmoke’s Matt Dillon and High Noon’s Will Kane. He just bought the first two seasons of Little House on the Prairie on Blu-ray.

“These were just good guys, earnest good guys,” MacFarlane said. “I think that’s what’s missing from popular culture today. You can have edgy jokes, but it really becomes much more satisfying if you have a backbone of earnestness... People freak out cause they think, ‘God, if I’m a millimetre off and I come off sappy,’ it’s like, who cares, so what, most of America is far less cynical than we are on the coasts.”

Theron is partial to the landscapes in westerns and to the element of survival in darker westerns like Unforgiven. Of the two, Theron, who grew up in South Africa, seemed better equipped for a dust-and-rain-whipped 70-day shoot in Utah and New Mexico than MacFarlane, who is from Kent, Connecticut. When she talked him into getting a Vitamin B-12 shot from the set medic, he bruised and she didn’t.

“That’s probably just circumstantial,” Theron said, of her apparently hardier constitution. “Now I’m just like an old princess. I’m not 20 anymore.”

Their friendship began as so many in Hollywood do — they have the same agents (Ari Emanuel and Greg Hodes at William Morris Endeavour). In life, as on screen, Theron is MacFarlane’s protective wing woman, rising to defend him against critics and calling him “up with the top 10 actors I’ve worked with.”

“Oh, go... yourself,” MacFarlane said, looking moved.

MacFarlane doesn’t seem like a guy who needs defending. He earned the clout to make a risky $40-million (Dh146 million) movie in the western comedy genre when Ted, his 2012 film about a grown man’s relationship with his stuffed teddy bear, became a surprise hit, grossing $549 million worldwide and spawning a sequel, due in 2015. Under a rich deal with 20th Century Fox Television, he is a prolific TV producer, continuing to make Family Guy, which was just renewed for its 13th season, as well as the animated show American Dad! and science documentary series Cosmos.

But MacFarlane’s comedy, laced with racial, ethnic and sexual jokes, has a way of getting under people’s skin — groups as divergent as the conservative Parents Television Council and the Gay and Lesbian Alliance Against Defamation have objected to different episodes of Family Guy, and feminists including Jane Fonda and Lena Dunham condemned the musical number of his Oscar hosting stint which featured women’s breasts.

A Million Ways to Die in the West has its share of politically incorrect humour as well. Along with physical comedy and a liberal use of flatulence sound effects, there’s a slave-shooting game at the county fair as well as jokes about Jews, Arabs, Native Americans and Chinese Americans.

The movie’s women — Theron’s sun-lit sidekick, Seyfried’s prissy ex-girlfriend, an industrious hooker played by Sarah Silverman — run the gamut. As with Mila Kunis’ character in Ted, Theron’s beauty and affection for the movie’s flawed leading man sometimes strains credulity but also helps his case. When Theron laughs at MacFarlane’s joke about her “cans,” she makes it OK for the audience to do so too. Or at least that’s the theory.

“It’s what Edith Bunker used to do for Archie,” MacFarlane said. “It makes it OK for you to like him.”

Theron said she was taken aback by the backlash to the Oscar skit for which she pre-taped a faux shocked reaction.

“The way he embraces women in his comedy and storytelling is unbelievably sweet,” Theron said.

She was quick to point out that ratings for MacFarlane’s Oscars were up over the previous year when Billy Crystal hosted, including a 20 per cent jump in the key 18-to-34 demographic.

“Many of the people who tuned in when he hosted... that age group never cared about the Oscars,” Theron said. “We know who the audience for our movies is. Yet we have an awards show that... doesn’t reflect our industry at all. I was like, yeah, finally we have a show that people want to go and see.”

MacFarlane said he feels blowback not from audiences but from journalists.

“The press is very easily offended,” he said. “It’s the outrage industry. The rest of the country, they’re fine. They’ll laugh. They’re OK with it. I don’t operate in the way that I want to please the critics. That’s like putting a puppet show on for your parents. You want as many people to see it as possible, as many people to enjoy it as possible, and the audience at large is OK with that stuff.”

Nonetheless he does test screen his films and occasionally makes tweaks. Test audiences balked at a funeral scene in A Million Ways to Die in the West, which MacFarlane cut but said he’ll put on the film’s DVD extras.

“If something is not working over and over, you can’t delude yourself that it’s funny,” he said.

Theron said she and MacFarlane were happy to keep each other from self-delusion on set as well.

“We had a very honest relationship,” Theron said. “It’s like when a friend tells you, ‘Don’t wear that shirt.’”