Larry Flynt, a ninth-grade dropout who built a $400 million empire of raunchy publications, strip clubs and “adult” shops around his sexually explicit magazine Hustler, and spent decades battling obscenity and libel charges as a self-promoting champion of freedom of the press, died on Wednesday at his home in Los Angeles. He was 78.

The cause was heart failure, said his brother, Jimmy Flynt.

To a nation in the throes of a sexual revolution in the 1970s, Mr. Flynt — defiant, outrageous, relentless — was at the nexus of a cultural and legal war in America: an unpopular hero to civil libertarians, the Devil incarnate to an unlikely alliance of feminists and morality preachers, a conundrum to judges and juries, and a purveyor of guilty secrets to legions of men slinking off from porn shops or the mailbox with brown paper parcels.

Hustler’s June 1978 cover caught the enigmas of a magazine that was at once salacious, satirical, perverse, decadent, gleefully immoral and hypocritical. It portrayed a woman upside down and half gone into a meat grinder, with a plate of hamburger below. A “seal of approval” noted: “Prime. Last All Meat Issue. Grade ‘A’ Pink.” A caption quoted Mr. Flynt, “We will no longer hang women up like pieces of meat.”

But, of course, Hustler was not serious. Starting with its first issue, in July 1974, and continuing nonstop for four decades, it displayed glossy, full-color photos of female genitalia, pictured naked women in demeaning poses and often depicted group sex and sex-toy fetishes.

ImageMr. Flynt planning an issue of Hustler with a photo editor, Edward Sonner, in 1977.Credit…Associated Press

Hustler articles offered “Larry Flynt on Sex in the White House,” “Coverbabe: New Slut in Town” and “Dirty Bedfellows: Explicit Photos & Sordid Tales From a Real Washington Intern.” But it was not all sex; there were also articles like “The Politics of Torture,” “Grenada Invasion: The True Story Behind Reagan’s ‘Facts’ ” and “Shocking New Facts in J.F.K. Assassination Coverup.”

Mr. Flynt’s most significant legal victory came in a long fight against the Rev. Jerry Falwell, the television evangelist and founder of the Moral Majority, who sued for $45 million for libel and emotional distress in 1983 after Hustler published a parody in which he reminisced about a sexual encounter with his mother in an outhouse.

A jury rejected the libel charge, saying the parody was obviously not factual, but awarded Mr. Falwell $200,000 for emotional distress. In 1988, the Supreme Court unanimously threw out the damages, calling the parody constitutionally protected political satire.

Mr. Flynt hailed the decision as the most important First Amendment victory since the obscenity ban on James Joyce’s “Ulysses” was overturned in the 1930s.

For all Mr. Flynt’s notoriety, his image as a defender of free speech was buoyed in 1996 with the Milos Forman film “The People vs. Larry Flynt,” which portrayed him as a kind of American folk hero, a smut peddler wrapped in the stars and stripes. Woody Harrelson was nominated for an Oscar for his performance as Mr. Flynt. The film won raves from many critics and most, though not all, civil libertarians.

But the feminist Gloria Steinem wrote a scathing denunciation on the Op-Ed page of The New York Times. “A pornographer is not a hero,” she said. “Hustler is depicted as tacky at worst, and maybe even honest for showing full nudity. What’s left out are the magazine’s images of women being beaten, tortured and raped, women subject to degradations from bestiality to sexual slavery.”

The images featured in Hustler were certainly graphic and often violent: Women were depicted crawling at the end of a dog leash, nailed to a cross, bagged like a deer and bound to a luggage rack. One cover showed a woman’s head in a gift box.

ImageMr. Flynt in 1977 at a free-speech rally in Ohio that he organized.Credit…Associated Press

Hustler claimed a monthly circulation of three million in the mid-1970s, though Forbes said it peaked at two million in 1976. With explicit sex on cable television, on DVD and on the internet, its circulation fell sharply in the ’80s and ’90s. In 1997, The Times said that Hustler’s press runs were under a million, but that half the newsstand copies were being returned unsold. In 2015, Mr. Flynt cited a circulation of 500,000.

The magazine’s revenues for years financed numerous Flynt enterprises: scores of magazines, some mainstream but mostly pornographic, including Taboo, Barely Legal and Asian Fever, whose number and nature varied over time; Hustler strip clubs in a dozen cities; and perhaps an equal number of Hustler chain stores that sold pornographic videos, as well as clothing, magazines and sex toys.

Mr. Flynt also owned a casino in Gardena, Calif.; operated websites that sold pornography; and licensed the Hustler name to magazines and other sex-oriented businesses in Canada, Britain, South Africa and Australia. His major profit centers included Hollywood studios that produced pornographic films, videos and cartoons, many with violent and misogynistic themes.

A 1983 study financed by the Justice Department and conducted by Judith Reisman, the conservative author and academic, found that thousands of cartoons in Hustler, as well as its competitors Playboy and Penthouse, depicted rape, botched abortions and children in sexual poses. “Chester the Molester,” a long-running Hustler cartoon feature about a pedophile, was denounced by many critics, but Mr. Flynt defended it as bawdy social satire.

The value of the Flynt empire was murky. It was privately held and not obliged to disclose finances. Mr. Flynt gave estimates of up to $700 million, but financial experts said his fortune varied widely over time with economic conditions, and the 2015 consensus put his net worth at about $400 million.

ImageMr. Flynt at his home in Ohio in 1978. That year he was shot near a courthouse by a sniper while he was on trial on an obscenity charge.Credit…Associated Press

Mr. Flynt, who once walked into a federal court wearing a diaper made from an American flag, thrust himself into the spotlight with drumbeat regularly — ridiculing conservative religious leaders, chronicling the sexual peccadilloes of politicians, arousing anger and amusement with parodies of patriotism, and assaulting the dignity of cultural icons.

In 1975, a year after it began publishing, Hustler drew international attention with the publication of nude photographs of Jacqueline Kennedy Onassis, taken by a paparazzo as she sunbathed on an Aegean beach. Mr. Flynt bought the pictures for $18,000 and quickly sold a million copies of the issue that featured them.

Mr. Flynt was prosecuted in 1976 for the first time on obscenity and organized-crime charges for selling obscene material in Cincinnati. Charles Keating, later convicted in a notorious savings and loan scandal, had founded Citizens for Decent Literature and led public outrage over the case. Mr. Flynt lost on both counts and was sentenced to seven to 25 years. But he served only six days, and the conviction was overturned on grounds of prosecutorial misconduct and judicial bias. The case spotlighted Cincinnati as a bastion of conservatism and Mr. Flynt as a dubious champion of free speech.

After being approached in 1977 by the evangelist Ruth Carter Stapleton, President Jimmy Carter’s sister, Mr. Flynt announced that he had become a born-again Christian, saying he had had a vision of God while airborne in his jet with Ms. Stapleton. He banned smoking at Hustler, gave the staff a raise, began a carrot juice diet and vowed to “hustle for God.” But he soon resumed his ventures and vices, calling himself an atheist.

In 1978, while on trial in Lawrenceville, Ga., on an obscenity charge, he was shot near the courthouse by a sniper who fled. Mr. Flynt’s legs were permanently paralyzed, and he spent the rest of his life using a gold-plated wheelchair. The assailant, Joseph Paul Franklin, a white supremacist who objected to Hustler’s portrayal of interracial couples, was captured in 1980. He was never tried for shooting Mr. Flynt, but confessed to a series of murders and was executed in Missouri in 2013.

In later years, many obscenity cases were brought against Mr. Flynt. He lost a few on jurisdictional or privacy grounds. But most foundered on the Supreme Court’s restrictive 1973 test defining obscenity as prurient, patently offensive material devoid of scientific, literary, artistic, political or social value, and taken as a whole in violation of subjective “community standards” — which meant it might play in Times Square, but not in Cincinnati circa 1976.

ImageMr. Flynt’s would-be assassin, Joseph Paul Franklin, was captured in 1980. Mr. Flynt’s legs were permanently paralyzed, and he spent the rest of his life using a wheelchair.Credit…Associated Press

Mr. Flynt’s interpretation was simpler. “If the First Amendment will protect a scumbag like me,” he said, “then it will protect all of you. Because I’m the worst.”

Larry Claxton Flynt Jr. was born in Lakeville, Ky., on Nov. 1, 1942, the oldest of three children of Larry Claxton Flynt, a sharecropper, and Edith (Arnett) Flynt. After his sister, Judy, died of leukemia in 1951, the family shattered. His parents divorced. Larry lived with his mother; his brother, Jimmy, lived with a grandmother.

At 15, Larry quit school in Salyersville, Ky., and with a phony birth certificate joined the Army. After his discharge, he bootlegged liquor, and in 1960 he joined the Navy and became a radar operator.

Discharged in 1964, he bought a bar in Dayton, Ohio, from his mother for $1,800 and used the profits to buy two more bars, then opened his first Hustler Club, with nude hostess-dancers.

In the late 1960s he opened Hustler strip clubs in Akron, Cleveland, Columbus, Toledo and Cincinnati. To promote his businesses, he created a newsletter featuring nude women. In 1974, it became Hustler magazine.

Playboy, Penthouse and other competitors crowded the newsstands, and Hustler struggled in its first year, partly because distributors and wholesalers balked at handling it. But the pictures of Mrs. Onassis made Hustler infamous overnight, and made Mr. Flynt a millionaire.

ImageMr. Flynt in his office in Beverly Hills, Calif., in 2003, when he announced his candidacy for governor of California. He built an empire of smut around his magazine and later presented himself as a champion of free speech.Credit…Monica Almeida/The New York Times

He was married five times. His first three marriages all ended in divorce. In 1976 he married Althea Leasure, who had helped start his businesses. She contracted AIDS and in 1987 drowned in a bathtub. In 1998 he married Elizabeth Berrios. He had five children. One, Lisa Flynt, died in a car accident in 2014.

In addition to his wife and brother, he is survived by his other children — T.J. Flynt, Theresa Flynt, Tonya Flynt-Vega and Larry Flynt Jr. — and many grandchildren.

Mr. Flynt published a memoir, “An Unseemly Man: My Life as a Pornographer, Pundit, and Social Outcast” (written with Kenneth Ross), in 1996. He was the subject of a documentary directed by Joan Brooker-Marks, “Larry Flynt: The Right to Be Left Alone,” in 2007. With David Eisenbach, he wrote, “One Nation Under Sex” (2011), about former presidents. After Mr. Falwell’s death in 2007, Mr. Flynt said that despite their differences they had become friends. “I always appreciated his sincerity,” he told The Los Angeles Times, “even though I knew what he was selling and he knew what I was selling.”

Alex Traub and Isabella Paoletto contributed reporting.

For the first time, a drug has been shown so effective against obesity that patients may dodge many of its worst consequences, including diabetes, researchers reported on Wednesday.

The drug, semaglutide, made by Novo Nordisk, already is marketed as a treatment for Type 2 diabetes. In a clinical trial published in the New England Journal of Medicine, researchers at Northwestern University in Chicago tested semaglutide at a much higher dose as an anti-obesity medication.

Nearly 2,000 participants, at 129 centers in 16 countries, injected themselves weekly with semaglutide or a placebo for 68 weeks. Those who got the drug lost close to 15 percent of their body weight, on average, compared with 2.4 percent among those receiving the placebo.

More than a third of the participants receiving the drug lost more than 20 percent of their weight. Symptoms of diabetes and pre-diabetes improved in many patients.

Those results far exceed the amount of weight loss observed in clinical trials of other obesity medications, experts said. The drug is a “game-changer,” said Dr. Robert F. Kushner, an obesity researcher at Northwestern University Feinberg School of Medicine, who led the study. “This is the start of a new era of effective treatments for obesity.”

Dr. Clifford Rosen of Maine Medical Center Research Institute, who was not involved in the trial, said, “I think it has a huge potential for weight loss.” Gastrointestinal symptoms among the participants were “really marginal — nothing like with weight loss drugs in the past,” added Dr. Rosen, an editor at the New England Journal of Medicine and a co-author of an editorial accompanying the study.

For decades, scientists have searched for ways to help growing numbers of people struggling with obesity. Five currently available anti-obesity drugs have side effects that limit their use. The most effective, phentermine, brings about a 7.5 percent weight loss, on average, and can be taken only for a short time. After it is stopped, even that amount of weight is regained.

The most effective treatment so far is bariatric surgery, which helps people lose 25 percent to 30 percent of body weight, on average, noted Dr. Louis Aronne, an obesity researcher at Weill Cornell Medicine in New York who advises Novo Nordisk and studies semaglutide.

But surgery is an invasive solution that permanently alters the digestive system. Only 1 percent of those who qualify go through with the procedure. Instead, most obese people try diet after diet with disappointing results.

The semaglutide study confirms what scientists already know, Dr. Kushner said: Willpower is not enough. In the new trial, participants who received the placebo and diet and exercise counseling were unable to see any significant difference in their weight.

Generally, insurers have refused to pay for the weight-loss drugs on the market. Semaglutide is likely to be expensive. The lower dose used to treat diabetes carries an average retail price of nearly $1,000 a month. (Insurers usually pay for diabetes drugs, Dr. Kushner noted.)

Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and a member of Novo Nordisk’s advisory board, said the effectiveness of semaglutide was “phenomenal” and that the trial results may lead insurers to cover it.

Semaglutide is a synthetic version of a naturally occurring hormone that acts on appetite centers in the brain and in the gut, producing feelings of satiety. A high-dose regimen of the drug has not been studied long enough to know if it has serious long-term consequences.

And it is expected that patients would have to take it for a lifetime to prevent the weight loss from coming back.

Qiana Mosely, who lives in Chicago, spent years trying to lose weight with diets and drugs, but to no avail. Then Ms. Mosely joined the semaglutide trial and lost 40 pounds, about 15 percent of her weight.

Ms. Mosely didn’t know until recently whether she was getting the drug or the placebo. Even though she was trying to eat well and exercise, her weight “was dropping too fast,” she said. “It had to be the meds.”

She experienced no side effects, she said. But when the trial ended and she no longer received the drug, the weight started coming back. “I was so sad,” she said. She is eager to resume taking the drug once it’s available.

After spending years courting Bruce Springsteen to appear in his first commercial, Jeep took down the ad on Wednesday after news broke that the rock legend had been charged with drunken driving in November.

The two-minute spot, which featured Mr. Springsteen in the rural middle of the country, urging unity from a white Jeep, was made last month and aired during the Super Bowl on Sunday. Time for the broadcast, the biggest television event of the year, cost most advertisers $5.5 million for 30 seconds.

The charges against Mr. Springsteen, which included reckless driving and driving while intoxicated in New Jersey on Nov. 14, became public on Wednesday. His first virtual court appearance will likely occur toward the end of February.

Jeep removed the Super Bowl ad, which was made by a creative team chosen by Mr. Springsteen, from its Twitter feed and YouTube page. The commercial was the second-most-watched game-day spot on YouTube on Sunday night, behind Amazon’s ad and ahead of commercials by Cadillac and Uber Eats, according to the platform.

In a statement, Jeep said, “It would be inappropriate for us to comment on the details of a matter we have only read about and we cannot substantiate. But it’s also right that we pause our Big Game commercial until the actual facts can be established.”

“Its message of community and unity is as relevant as ever,” the company said. “As is the message that drinking and driving can never be condoned.”