Skincare Firm Vows To Rid 'Ozempic Face' In New Marketing Push

 One side effect of GLP-1 medications for weight loss is "Ozempic Face." This happens when the rapid loss of body fat produces a hollowed-looking face, wrinkles, sunken eyes, and changes in the size of the lips, cheeks, and chin. To counter this, skincare companies are ramping up the marketing of products to 'fix' this side effect as these blockbuster drugs sweep the nation. 

Swiss skincare company Galderma Group's Chief Executive Officer Flemming Ornskov told Bloomberg in an interview after this week's first-quarter earnings that its skin treatments and dermal fillers "should be able to restore this [Ozempic Face]." 

"I think that will be another growth wave in that space, which I will make sure to capture," Ornskov said. 

Has Wall Street woken up to Galderma's ability to indirectly capitalize on the weight loss craze?

Goldman's GLP-1 winners basket still shows a strong upward trend. 

Novo Nordisk A/S's blockbuster treatments, Ozempic for diabetes, and Wegovy for weight loss, are both two names for the same drug: semaglutide. The FDA approved Ozempic for diabetes in 2017 and Wegovy for obese people in 2021. 

The issue with Wegovy is its effectiveness. Within four weeks of treatment, the average weight loss is around 5% of body weight, increasing to 8% after two months. Semaglutide, the active ingredient, significantly decreases appetite and hunger.

"If weight is lost in a more gradual way, these changes may not be as noticeable. It's the faster pace of weight loss that occurs with GLP-1 drugs that can make facial changes more obvious," Harvard Health Publishing wrote in a note. 

Here are real-world examples of Ozempic Face: 

Google searches for "Ozempic Face" are soaring to record highs. 

For those who can afford Ozempic Face, try also walking around in $1,000 'dirty' Gucci sneakers to complete your look as a starved homeless person - or unvetted, starved illegal alien. 

Instead of being the guinea pig for the pharma-industrial complex, why not just put down the processed foods from the food-industrial complex and just go outside for a jog? 

At this rate, with a new study from Kaiser Family Foundation showing upwards of 3.6 million people will be subsidized for the miracle weight loss drugs, this could ultimately accelerate the bankrupting of Medicare.  

https://www.zerohedge.com/markets/skincare-firm-vows-rid-ozempic-face-new-marketing-push

How Do You Solve a Problem Like Mike Johnson?

 The Sound of Music was an iconic movie for my generation. We watched it at movie theaters when it made its yearly appearance, then eventually on television. If you missed it, you had to wait a year until it was rebroadcast as there was no video on demand as there is today.

It was a fun movie featuring sing-a-long music, romance, mischief, and a realistic view of jackbooted Nazis destroying a beautiful country. There was no same-sex marriage, no transgenders, no mention of global warming, diversity, wokeness, or any other message permeating current movies and television shows.

Naturally, the media bristled, especially since the jackbooted thugs in the movie are now the modern Democrat party, in all three letter government agencies, harassing and imprisoning their political opponents.

The Daily Beast claimed, “Everyone hated The Sound of Music”, just as they claim that everyone hates Donald Trump, white men, Christians, heterosexuals, gun owners, patriots, and the like, all of which are modern-day Captain Von Trapp’s.

One popular song was “How do you solve a problem like Maria?” Fifty years later, we have a new Maria, a “flibbertijibbet” House Speaker named Mike Johnson. And a problem he is. Can he be solved?

Johnson replaced Kevin McCarthy, who broke numerous promises to his caucus, including the full release of January 6 videos, a proper budget process as opposed to “omnibus” bills that Congress had little or no time to review, and bringing each spending bill to Congress for a separate vote.

McCarthy was replaced by a compromise choice of Mike Johnson. As The Who sang, “Meet the new boss, same as the old boss”, Speaker Johnson is the new boss, also pushing massive omnibus spending bills, not releasing all the January 6 entrapment evidence, supporting continued warrantless spying on Americans, and pushing endless aid to secure the borders of countries thousands of miles away from America while leaving America’s borders wide open.

He follows the pattern of past GOP Speakers—Boehner, Ryan, McCarthy, and now Johnson. It seems Republican voters continue to ask and vote for a medium-rare steak only to be served a burnt, inedible slab of meat.

At the time of this writing, 100 House Republicans, along with all Democrats, voted “Ukraine First”, leaving America Last. As Senator Rand Paul tweeted,

Ukrainian flags fly in the chamber of the UNITED STATES House of Representatives as they vote to send more of your hard-earned money to a corrupt foreign regime. And just like that they shout “UKRAINE! UKRAINE!” while happily working to secure Ukraine’s borders, not ours.

The bill also included billions for Israel and Taiwan, while 78 percent of Americans are living paycheck to paycheck, and 300,000 known illegal migrants enter the U.S. each month.

Ukrainian President Volodymyr Zelensky said he was “personally” grateful to “Speaker Mike Johnson for the decision that keeps history on the right track,” meaning the deaths of tens of thousands more Ukrainian men.

Is the family of Laken Riley, brutally murdered by an illegal alien, “personally grateful” to Speaker Johnson for his tough stand on our open border?

So much for Congress representing the American people. Do Americans think borrowing money from China, since America is broke, and sending it 4,000 miles away, is a good thing?

"This is the best possible product that we can get under these circumstances, to take care of these really important obligations," Johnson said Friday. Does he have any obligation to struggling Americans? Apparently not.

The Speaker is also a believer in white privilege and systemic change. What difference would it make if AOC or Maxine Waters took Johnson’s place as Speaker? Democrats are advancing their agenda with a Republican House Speaker. They want to keep Johnson right where he is.

Johnson is playing a dangerous game, defying much of his GOP caucus: “Republican House Speaker Mike Johnson, putting his job on the line, relied on Democratic support this week to set up a series of votes on three aid bills.”

Rep. Marjorie Taylor Greene wants to remove Speaker Johnson via a “motion to vacate.”  She has some support within her caucus, but then what?

With a one-vote majority, the GOP is playing a dangerous game. If they remove Johnson, maybe he will quit the House, as did McCarthy and GOP Reps. Ken Buck and Mike Gallagher, leaving Democrats in charge.

Former President Trump muddied the waters with his support of Johnson, “Trump says he thinks Speaker Mike Johnson is ‘doing a very good job’ amid ouster threat from Marjorie Taylor Greene.”

I doubt this is some form of 5D chess from Trump; it is only the simple reality that if Johnson is ousted and Democrats take control of the House, Trump's November election is over.

Remember the U.S. Supreme Court decision on “insurrection” claimed by the Colorado Supreme Court? The March 4 decision stated:

The Constitution empowers Congress to prescribe how those determinations should be made. The relevant provision is Section 5, which enables Congress, subject of course to judicial review, to pass “appropriate legislation” to “enforce” the Fourteenth Amendment.

In other words, Congress, by a simple majority, can pass a bill claiming that Trump is disqualified from the election due to being an “insurrectionist.” That would be the first order of business by a Democrat-controlled House. The Senate would pass the House bill and President Biden would sign it.

If you don’t believe the Democrats would try to disqualify Trump in this manner, a bill introduced by Democrat Rep. Jamie Raskin is already teed up.

Per Axios:

Raskin pointed to legislation he introduced with Rep. Debbie Wasserman Schultz (D-Fla.) in 2022 creating a pathway for the Justice Department to sue to keep candidates off the ballot under the 14th Amendment.

"We are going to revise it in light of the Supreme Court's decision," Raskin said.

Raskin suggested the bill would be paired with a resolution declaring Jan. 6 an "insurrection" and that those involved "engaged in insurrection."

The SCOTUS decision mentioned, “Subject of course to judicial review.” Would that stop such a scheme? Why would SCOTUS block such an act of Congress that they green-lighted in their recent decision?

This would explain Trump supporting Johnson. Does Rep. MTG realize how this could play out? Is she acting out of principle, or is this a backhanded way of undermining Trump? This is where the 5D chess machinations come in. Washington, D.C., is indeed a swamp.

While I would love to see a principled conservative America First Speaker of the House and a similar GOP caucus, we got what we got, and some GOP members “cutting off their nose to spite their face” is not a good strategy.

Keep the House in GOP control with Johnson in charge and elect a new Speaker next year. Losing the House means losing Trump and any hope of rescuing America from its rapid decline.

A Democrat Congress and White House would stack the Supreme Court and rewrite the Bill of Rights. The border will remain open with amnesty and voting rights for all illegals. Election laws will be changed, despite this being under states’ jurisdiction per the Constitution. That didn’t matter in 2020, so why would it matter in 2024?

How do we solve a problem like Speaker Johnson? Removing him now isn’t the answer, as the alternative may be far worse.

As with Maria, “Many a thing you know you'd like to tell her. Many a thing she ought to understand.”

I’m sure Speaker Johnson understands. He is driving through treacherous mountains with no guardrails. Is he compromised as some in the Capitol are?

The nuns thought Maria “a clown.” Many think the same of the Speaker and many of his America-Last GOP caucus. So let the Congressional circus go on!

Brian C. Joondeph, M.D., is a physician and writer. Follow me on Twitter @retinaldoctor, Substack Dr. Brian’s Substack, Truth Social @BrianJoondeph, and LinkedIn @Brian Joondeph.

https://www.americanthinker.com/articles/2024/04/how_do_you_solve_a_problem_like_mike_johnson.html

Obama Gets Around to Commenting on Hamas at Columbia

 As Columbia University’s most prominent alum, former president Barack Obama would seem to have a moral obligation to speak about what is arguably the most visible outbreak of antisemitism on American soil in his lifetime.

I refer here to the occupation of Obama’s alma mater by Hamas-supporters who have been openly threatening Jewish students, chanting “Kill all Zionists,” and shouting racial slurs like “pig.”

As I sat down to write this, five days into the protest, Obama had said not a word.

By contrast, Obama was tweeting about the August 2017 Antifa/white nationalist brouhaha in Charlottesville, Virginia before the day was through.

“No one is born hating another person because of the color of his skin or his background or his religion,” Obama tweeted in the evening of August 12. “People must learn to hate, and if they can learn to hate, they can be taught to love, for love comes more naturally to the human heart than its opposite.”

At the time, this was the most “liked” tweet in Twitter (now X) history.

In the last five days, Obama tweeted about Earth Day twice, about a book on healthy lifestyles, and about the death of Florida politico Bob Graham. But not a word about Columbia, at least not until I started writing.

“One minute ago” — is the NSA that good? — Obama weighed in with a photo of himself and Michelle at a traditional seder meal from days gone by. In this tweet, marking the beginning of Passover, there is no talk of hate, no mention of Hamas, no reference to Columbia.

“And in a time when there’s been so much suffering and loss in Israel and Gaza,” he writes in his fortune cookie prose, “let’s reaffirm our commitment to the Jewish people, and people of all religions, who deserve to feel safe and secure wherever they live and practice their faith.”

That should rein in the little darlings at Columbia, no?

No, not at all.

Like all respectable Democrats, Obama is conflicted about the Hamas protests, only more so. As a fellow traveler in the world of Islam, Obama has had to work hard to keep his roots from showing. He has barely succeeded. In a lengthy statement in October, Obama made a few perfunctory remarks about the “unspeakable brutality” perpetrated by Hamas on October 7, but he reserved very nearly all his finger-wagging for Israel.

He called on Jews to acknowledge that many Palestinians “were not only displaced when Israel was formed but continue to be forcibly displaced by a settler movement that too often has received tacit or explicit support from the Israeli government.” He made the dubious claim as well that “Palestinian leaders who’ve been willing to make concessions for a two-state solution have too often had little to show for their efforts.” In short, he scolded Israelis for wanting to defend themselves against people who like to brag on video about their “unspeakable brutality.”

From the beginning, the media have allowed Obama to conceal his easy tolerance of antisemitism. One journalist who came to Obama’s aid, unapologetically at that, was photographer and occasional National Public Radio (NPR) commentator Askia Muhammad.

In January 2018, as a way of promoting his new book, Muhammad shared with the world a photo he had taken in 2005 at a Black Congressional Caucus event. In the center of the photo is a smiling Barack Obama. Standing right next to him, also smiling broadly, is Nation of Islam honcho Louis Farrakhan. Sensing what might generously be called “bad optics,” a Black Caucus member stopped Muhammad even before he left the building.

“I gave the picture up at the time and basically swore secrecy,” Muhammad admitted thirteen years later. “But after the nomination was secured and all the way up until the inauguration; then for eight years after he was president, it was kept under cover.”

When asked whether he thought the photo, if revealed, would have made a difference in the 2008 campaign, Muhammad said, emphatically, “It absolutely would have made a difference.”

The Los Angeles Times violated just about all journalistic canons to bail Obama out in 2008 when it mattered most. In April of that year, the Times secured a copy of a video recorded at a dinner held in Chicago in 2003 on behalf of Obama’s close friend, Rashid Khalidi. As liberal David Garrow points out in his Obama biography, Rising Star, the Obamas, the Khalidis, Bill Ayers, and his wife Bernardine Dohrn dined together almost weekly before Obama felt the need — with the media’s able assistance — to bury those relationships.

The occasion was Khalidi’s imminent departure from Chicago for Columbia University in New York. In 2008, his friendship with Obama posed obvious problems for the candidate. Khalidi would deny he was a spokesman for the lethal Palestinian Liberation Organization, but he was close enough to the PLO to give the rumors merit.

In his account of the dinner, Peter Wallsten of the Times reported a few of the provocative toasts offered to the departing Khalidi. One of the dinner guests compared “Zionist settlers on the West Bank” to Osama bin Laden. Another guest recited a poem accusing Israel of terrorism. For his part, Obama was quoted as thanking Khalidi for offering “consistent reminders to me of my own blind spots and my own biases.”

What Weather Underground alums Ayers and Dohrn might have said in Obama’s presence was not reported. The Times absolutely refused to air the videotape it had in its possession or let any other party see it. Obama’s reaction to the group’s virulent obsession with Jews and Israel was lost for the ages.

As to Khalidi, last week, an undercover reporter caught him saying what the media would rather he did not. The reporter was posing as a student appalled by the campus’s “Zionistic culture,” a comment that Khalidi affirmed. Apparently, even Columbia’s tepid response to widespread Jew-baiting troubled him.

“We have an antisemitism task force because everybody on the other side has howled their head off if somebody has so much as looked sideways at them,” said the delusional Khalidi. He called the task force “yet another blow” against his allies on campus. “I mean, they picked bigots, fanatics, right-wingers, and extremists,” he said. “I mean, it’s a scandal, and you can’t say anything.”

In the real world, Khalidi can say just about anything he likes with impunity. Until November, at least, Obama has got to be more careful.

https://www.americanthinker.com/articles/2024/04/obama_gets_around_to_commenting_on_hamas_at_columbia.html

At a Sheetz Photo Op, Joe Biden Accidentally Shows His Hand

 Politicians on campaign sweeps visit lots of places.

Ice cream shops, diners, factories, state fairs – the opportunities are endless.  You might only shake hands with five or ten people there, but if a photo makes it on the evening news or the morning paper, tens of thousands of people may see it.  And nothing beats free publicity.

Most of these quick campaign stops are interchangeable. It doesn’t matter whether it’s a gift shop or a fast food place, all that matters is some fluffy, issue-free reporting on the evening news.

Something went very wrong with that system on Wednesday, April 17, 2024.  Instead of the human interest story of Joe Biden buying sandwiches for steelworkers, the fact that the photo op took place at a Sheetz gas station and convenience store turned out to be the news story of the week, especially in Appalachia where Sheetz employs some 25,000 people, a region where hundreds of thousands of working folks of all ages got their start in that kind of job over the years.

The very same day that Scranton Joe was glad-handing potential voters at a Sheetz location in the swing state of Pennsylvania, Beltway Joe’s deputies at the EEOC, back home in the very non-swing jurisdiction of Washington D.C. were putting the final touches on a ridiculous federal lawsuit against Sheetz.

On Thursday, Americans were confronted with two very different stories: Joe Biden lauding the local Sheetz store as quintessential Americana, and Joe Biden attacking a private business on trumped-up charges, looking for every opportunity to beat up a successful corporation.

The dichotomy reminds one of the perennial Jekyll-and-Hyde nature of the politicians of the swamp:

While Jekyll’s smiling figure shakes your hand and kisses your baby at election time, Hyde’s mind is always rooted in the bureaucracy – working 24/7 to use the power of government, to destroy your business, your neighborhood, your environment, your life.

The job of the campaign, the press, the education system and the pop culture is to hide that dichotomy so no voter ever notices it.  The timing on this particular incident made that job more difficult than usual.

Much of the reporting on this unusual circumstance has focused on half-heartedly ribbing the Biden campaign:  Don’t these people check first?  Didn’t they think to see if the campaign stop was “politically correct” before putting it on the day’s agenda?  How incompetent can this team be if they’re siccing federal prosecutors on a business that the boss is visiting on a campaign swing?

But that’s exactly the wrong way to look at it.

No campaign should have to check out this sort of thing before scheduling a campaign swing, because this sort of occurrence really shouldn’t exist in the first place.

Our Founding Fathers never intended for our federal government to have this kind of power. The Constitution severely limits what the executive branch is allowed to do.  It can’t grow so strong that it can become tyrannical; it can’t grow so many tentacles that it can infest every part of the private sector.  It can’t have so many prosecutors that every American need fear harassment; it can’t have so many powers that it can choose from a wide array of prosecutorial options.  None of this is Constitutional.

In fact, the kind of prosecution in this particular case could never even have been imagined by the Framers.  Think about it:

The federal government has selected a private employer – one whose employees must work retail at all hours, often in remote locations, handling cash, responsible for thousands of dollars’ worth of merchandise, dealing with the public – and is prosecuting this company for using a criminal background check in its hiring process.  They just want to protect their sites, their customers, and their other employees by hiring the right people.  

Vulnerable people – both customers and fellow employees – will often be alone in the shop with these employees.  It would be irresponsible not to use criminal background checks in their hiring process.

In fact, hasn’t the value of criminal background checks been the Left’s claim for decades? They demand criminal background checks before rifles, handguns, or ammunition can bought or sold, because they know from the massive amount of crime in America (which grows and grows under Democrat governance) that we are all at risk from our fellow man, at all times.

If criminal background checks are appropriate for a gun shop, where practically everyone is armed and trained for self-defense already, then surely criminal background checks are appropriate for an often-empty store, often on the side of a highway where travelers and other defenseless strangers shop at all hours.

On what grounds does the current regime attack the Sheetz chain?  The Constitution only empowers the federal government to regulate interstate commerce when the states concerned have disagreements. Has any state objected to Sheetz’ hiring practices?  Does Pennsylvania differ with Maryland on how gas station chains operate? Do Ohio and Virginia disagree on the temperature at which their sandwiches are cooked? 

In fact, it’s patently clear that there are no Constitutional grounds whatsoever for the Biden regime’s war against Sheetz.  Their attack on the use of background checks to safeguard the public is purely political, a DEI assault, an attack against some poor business, probably chosen at random, so the Left’s politicians can show their voracious donors that such prosecutions are happening as ordered. 

The goal of the modern American Left is to keep the private sector in fear. 

Be afraid of the IRS tax audit, the EEOC hiring practices lawsuit, the ADA complaint about the accessibility of your elevators. Be terrified of the OSHA reportable, the EPA groundwater test, the DoT review of your trucking fleet’s log books.

This is the federal government under Joe Biden, Kamala Harris, and the modern Democrat party. This is how they want it.

In this unhinged world, Sheetz’ mistake was in having any hiring procedures at all. A rational employment policy is just too tempting a target for the Biden-Harris crowd.

Sheetz is concerned about the safety of their employees and customers, late at night or at a remote interstate exit. 

But as we can see from the prosecuting records in America’s Democrat-run big cities, the infestation of freely-operating gangs, and the open borders that have brought millions of foreign lawbreakers into the country these past three years, it’s patently obvious that the safety of American citizens is the last thing on the minds of a modern Democrat politician.

John F. Di Leo is a Chicagoland-based international transportation manager, trade compliance trainer and speaker. A one-time Milwaukee County Republican Party chairman, he has been writing a regular column for Illinois Review since 2009. Read his book on vote fraud (The Tales of Little Pavel) and his political satires on the current administration (Evening Soup with Basement Joe, Volumes I,  II, and III).

https://www.americanthinker.com/articles/2024/04/at_a_sheetz_photo_op_joe_biden_accidentally_shows_his_hand.html

BioMarin Surpasses Revenue and EPS Estimates

 

• Revenue: Reported at $648.8 million, marking a 9% increase year-over-year, slightly below the estimated $651.79 million.

• Net Income: GAAP net income surged to $88.7 million, a substantial 74% increase from the previous year, significantly exceeding the estimated $62.56 million.

• Earnings Per Share (EPS): GAAP diluted EPS reached $0.46, up 70% year-over-year, surpassing the estimated $0.35.

• Non-GAAP Performance: Non-GAAP diluted EPS reported at $0.71, an 18% increase year-over-year, indicating strong profitability excluding specific expenses.

• Product Performance: VOXZOGO revenue soared by 74% to $152.9 million, driven by a significant increase in the number of children treated.

• Research and Development: Focused investment in high-value programs, with increased R&D expenses supporting new indications for VOXZOGO and other key assets.

• Full-Year Guidance: Reaffirmed total revenue expectations and raised non-GAAP operating margin and EPS forecasts, reflecting confidence in continued growth and operational efficiency.

BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) released its 8-K filing on April 24, 2024, revealing a robust financial performance for the first quarter of 2024. The company reported total revenues of $648.8 million, a 9% increase year-over-year, which surpassed the analyst's expectation of $651.79 million. Notably, GAAP diluted earnings per share (EPS) stood at $0.46, a significant 70% increase from the previous year, and non-GAAP diluted EPS was $0.71, up 18% year-over-year, both exceeding the estimated earnings per share of $0.35.

https://finance.yahoo.com/news/biomarin-pharmaceutical-inc-bmrn-q1-213335734.html

Viking results, update

 

• Results From Phase 2 VENTURE Trial of GLP-1/GIP Agonist VK2735 in Obesity Demonstrated Up to 13.1% Placebo-Adjusted Weight Loss (14.7% From Baseline) at 13 Weeks; Shown to be Safe and Well-Tolerated
  
  
• Results From Phase 1 Trial of Oral VK2735 Demonstrated Promising Safety and Tolerability With Up to 3.3% Placebo-Adjusted Weight Loss (5.3% From Baseline) at 28 Days
  
  
• 52-Week Histology Results From Phase 2b VOYAGE Study Evaluating VK2809 for the Treatment of NASH and Fibrosis Expected in 2Q24
  
  
• Completed Public Offering of Common Stock Raising Gross Proceeds of Approximately $630 Million; Quarter-End Cash Position of $963 Million

Management will host a conference call to discuss Viking's first quarter 2024 financial results today at 4:30 pm Eastern.  To participate in the conference call, please dial (844) 850-0543 from the U.S. or (412) 317-5199 from outside the U.S.  In addition, following the completion of the call, a telephone replay will be accessible until May 1, 2024, by dialing (877) 344-7529 from the U.S. or (412) 317-0088 from outside the U.S. and entering conference ID # 8359459.  Those interested in listening to the conference call live via the internet may do so by visiting the Webcasts page of Viking's website at http://ir.vikingtherapeutics.com/webcasts.  An archive of the webcast will also be available on the Webcasts page of Viking's website for 30 days.

https://www.prnewswire.com/news-releases/viking-therapeutics-reports-first-quarter-2024-financial-results-and-provides-corporate-update-302126602.html

In spinal cord injury, neurons can harm metabolism; common drug may prevent some effects

 Conditions such as diabetes, heart attack, and vascular diseases commonly diagnosed in people with spinal cord injuries can be traced to abnormal post-injury neuronal activity that causes abdominal fat tissue compounds to leak and pool in the liver and other organs, a new animal study has found.

After discovering the connection between dysregulated neuron function and the breakdown of triglycerides in fat tissue in mice, researchers found that a short course of the drug gabapentin, commonly prescribed for nerve pain, prevented the damaging metabolic effects of spinal cord injury.

Gabapentin inhibits a neural protein that, after the nervous system is damaged, becomes overactive and causes communication problems—in this case, affecting sensory neurons and the abdominal fat tissue to which they're sending signals.

"We believe there is a maladaptive reorganization of the sensory system that causes the fat to undergo changes, initiating a chain of reactions—triglycerides start breaking down into glycerol and free fatty acids that are released in circulation and taken up by the liver, the heart, the muscles, and accumulating, setting up conditions for insulin resistance," said senior author Andrea Tedeschi, assistant professor of neuroscience in The Ohio State University College of Medicine.

"Through administration of gabapentin, we were able to normalize metabolic function."

The study is published in Cell Reports Medicine.

Previous research has found that cardiometabolic diseases are among the leading causes of death in people who have experienced a spinal cord injury. These often chronic disorders can be related to dysfunction in visceral white fat (or adipose tissue), which has a complex metabolic role of storing energy and releasing fatty acids as needed for fuel, but also helping keep blood sugar levels at an even keel.

Earlier investigations of these diseases in people with neuronal damage have focused on adipose tissue function and the role of the sympathetic nervous system—nerve activity known for its "fight or flight" response, but also a regulator of adipose tissue that surrounds the abdominal organs.

Instead, Debasish Roy—a postdoctoral researcher in the Tedeschi lab and the first author of the paper—decided to focus on sensory neurons in this context. Tedeschi and colleagues have previously shown that a neuronal receptor protein called alpha2delta1 is overexpressed after spinal cord injury, and its increased activation interferes with the post-injury function of axons, the long, slender extensions of nerve cell bodies that transmit messages.

In this new work, researchers first observed how sensory neurons connect to adipose tissue under healthy conditions and created a spinal cord injury mouse model that affected only those neurons—without interrupting the sympathetic nervous system.

Experiments revealed a cascade of abnormal activity within seven days after the injury in neurons—though only in their communication function, not their regrowth or structure—and in visceral fat tissue. Expression of the alpha2delta1 receptor in sensory neurons increased as they over-secreted a neuropeptide called CGRP, all while communicating through synaptic transmission to the fat tissue—which, in a state of dysregulation, drove up levels of a receptor protein that engaged with the CGRP.

"These are quite rapid changes. As soon as we disrupt sensory processing as a result of spinal cord injury, we see changes in the fat," Tedeschi said. "A vicious cycle is established—it's almost like you're pressing the gas pedal so your car can run out of gas but someone else continues to refill the tank, so it never runs out."

The result is the spillover of free fatty acids and glycerol from fat tissue, a process called lipolysis, that has gone out of control. Results also showed an increase in blood flow in fat tissue and recruitment of immune cells to the environment.

"The fat is responding to the presence of CGRP, and it's activating lipolysis," Tedeschi said. "CGRP is also a potent vasodilator, and we saw increased vascularization of the fat—new blood vessels forming as a result of the spinal cord injury. And the recruitment of monocytes can help set up a chronic pro-inflammatory state."

Silencing the genes that encode the alpha2delta1 receptor restored the fat tissue to normal function, indicating that gabapentin—which targets alpha2delta1 and its partner, alpha2delta2—was a good treatment candidate. Tedeschi's lab has previously shown in animal studies that gabapentin helped restore limb function after spinal cord injury and boosted functional recovery after stroke.

But in these experiments, Roy discovered something tricky about gabapentin: The drug prevented changes in abdominal fat tissue and lowered CGRP in the blood—and in turn prevented spillover of fatty acids into the liver a month later, establishing normal metabolic conditions. But paradoxically, the mice developed insulin resistance—a known side effect of gabapentin.

The team changed drug delivery tactics, starting with a high dose and tapering off—and stopping after four weeks.

"This way, we were able to normalize metabolism to a condition much more similar to control mice," Roy said. "This suggests that as we discontinue administration of the drug, we retain beneficial action and prevent spillover of lipids in the liver. That was really exciting."

Finally, researchers examined how genes known to regulate white fat tissue were affected by targeting alpha2delta1 genetically or with gabapentin, and found both of these interventions after spinal cord injury suppress genes responsible for disrupting metabolic functions.

Tedeschi said the combined findings suggest starting gabapentin treatment early after a spinal cord injury may protect against detrimental conditions involving fat tissue that lead to cardiometabolic disease—and could enable discontinuing the drug while retaining its benefits and lowering the risk for side effects.

More information: Debasish Roy et al, α2δ1-mediated maladaptive sensory plasticity disrupts adipose tissue homeostasis following spinal cord injury, Cell Reports Medicine (2024). DOI: 10.1016/j.xcrm.2024.101525

https://medicalxpress.com/news/2024-04-spinal-cord-injury-neurons-wreak.html