Posted on 07/10/2025 10:54:30 AM PDT by Red Badger
A new drug prevents weight gain and fatty liver by controlling magnesium in cells. It made mice stay slim despite lifelong exposure to an unhealthy diet. Credit: Stock
Scientists have unveiled a small-molecule drug that blocks weight gain and liver damage in mice forced to live on sugary, high-fat food.
The compound works by limiting magnesium inside mitochondria—the cell’s power plants—so energy keeps burning instead of stalling. Treated mice quickly slim down and show no signs of fatty-liver disease, hinting at a future therapy against obesity, heart trouble, and cancer tied to poor diets.
Breakthrough Drug Fights Fat and Liver Disease
Researchers at UT Health San Antonio, working with colleagues from the University of Pennsylvania and Cornell, have created a small-molecule drug that keeps mice from gaining weight or developing liver damage even when they eat a lifetime of sugary, high-fat food.
“When we give this drug to the mice for a short time, they start losing weight. They all become slim,” said Madesh Muniswamy, PhD, professor of medicine in the health science center’s Joe R. and Teresa Lozano Long School of Medicine. The study appears in Cell Reports.
“A drug that can reduce the risk of cardiometabolic diseases such as heart attack and stroke, and also reduce the incidence of liver cancer, which can follow fatty liver disease, will make a huge impact.”
Magnesium’s Hidden Role in Metabolism
The team began by asking how magnesium shapes metabolism—the way cells make and burn energy called ATP. Magnesium is the body’s fourth-most abundant charged mineral, vital for blood sugar control, blood pressure, and bone strength. Yet the scientists discovered that an excess of magnesium inside mitochondria, the cell’s “power plants,” actually slows energy production.
“It puts the brake on, it just slows down,” said co-lead author Travis R. Madaris, doctoral student in the Muniswamy laboratory at UT Health San Antonio.
When the researchers deleted MRS2, a gene that shuttles magnesium into mitochondria, the animals burned sugar and fat more efficiently. The mice stayed lean and healthy, with liver and fat tissue showing no trace of diet-induced fatty liver disease.
Man Stepping on Brake Pedal
Magnesium acts like a brake on energy production, researchers found. Credit: Shutterstock Drug CPACC Mimics Genetic Effect
The drug, which the researchers call CPACC, accomplishes the same thing. It restricts the amount of magnesium transfer into the power plants. In experiments, the result was again: skinny, healthy mice. UT Health San Antonio has filed a patent application on the drug.
The mice served as a model system of long-term dietary stress precipitated by the calorie-rich, sugary and fatty Western diet. The familiar results of this stress are obesity, type 2 diabetes and cardiovascular complications.
“Lowering the mitochondrial magnesium mitigated the adverse effects of prolonged dietary stress,” said co-lead author Manigandan Venkatesan, PhD, postdoctoral fellow in the Muniswamy lab.
Joseph A. Baur, PhD, of the University of Pennsylvania, and Justin J. Wilson, PhD, of Cornell, are among the collaborators. “We came up with the small molecule and Justin synthesized it,” Madaris said.
Major Health Impact Potential “These findings are the result of several years of work,” Muniswamy said. “A drug that can reduce the risk of cardiometabolic diseases such as heart attack and stroke, and also reduce the incidence of liver cancer, which can follow fatty liver disease, will make a huge impact. We will continue its development.”
Reference:
“Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress”
by Travis R. Madaris, Manigandan Venkatesan, Soumya Maity, Miriam C. Stein, Neelanjan Vishnu, Mridula K. Venkateswaran, James G. Davis, Karthik Ramachandran, Sukanthathulse Uthayabalan, Cristel Allen, Ayodeji Osidele, Kristen Stanley, Nicholas P. Bigham, Terry M. Bakewell, Melanie Narkunan, Amy Le, Varsha Karanam, Kang Li, Aum Mhapankar, Luke Norton, Jean Ross, M. Imran Aslam, W. Brian Reeves, Brij B. Singh, Jeffrey Caplan, Justin J. Wilson, Peter B. Stathopulos, Joseph A. Baur and Muniswamy Madesh, 27 February 2023, Cell Reports.
DOI: 10.1016/j.celrep.2023.112155
Funders of this project include the National Institutes of Health, the U.S. Department of Defense and the San Antonio Partnership for Precision Therapeutics.
A version of this article was originally published in April 2023.
And the side effects are.....???
And I'm guessing that a junk food diet is not high in Mg and therefore the excess Mg in the mitochondria is due to metabolism issues from being obese, not from food intake or MG intake.
I thought I read recently that magnesium helped to prevent dementia. Do I have to choose between being fat & getting Alzheimer’s? Decisions, decisions...
And the hairline? What’s that tell you? Just sayin’
Now that you mention it, all the dementia people I have known were not fat..................
Reading the story, this sounds like an anti-Magnesium drug.
Yes, for this guy though, I am chronically low on magnesium and potassium, so I have to take supplements. Good thing they are cheap.................
It sounds like this drug keeps the magnesium from getting into the mitochondria so you can have enough magnesium in the blood to do what the rest of the body needs without having enough in the mitochondria to block energy production.
But I’m not a scientist so I don’t even know if what I just wrote even makes sense. lol
They started off as 15 minute boring commercials back in the late 40s-early 50s.
bump
Seems to be on a loop. Wasn’t even paying attention to the TV last week and every time I looked up some skank was spraying his junk.
Yes and stop making the sofa your best friend.
“You are the fifth person who told me that in this thread. Thanks.”
You misread something you receive ten responses, you make a unique, fabulous observation, crickets.
You sure do like to use a lot of words to say nothing.
You beat me to it.
It seems neither of us was born yesterday.
Amen. I am in my 60s and was obese most of my adult life. I lost 50 lbs in my 30s, but quickly regained all of it and more. At 60, I decided I would like to see my grandkids grow up and realized it was now or never. It took me over a year and a half but I was able to lose more than 100 lbs and I have kept it off for almost a year so far.
The most important factor was walking an hour first thing every morning before eating breakfast, first dragging myself along and eventually working my way up to a slow 3-4 mph jog (60 year old joints preclude ever running any marathons). I also cut out all processed foods and sugar and reduced my caloric intake to approx 1,500 calories a day.
The first few months I dropped over 10 lbs per month. My weight loss slowed over time and after 9 months I was averaging less than 5 lbs a month. Some months I either wouldn't lose any weight at all or would gain 2-3 lbs. Once I reached my weight goal (what I weighed when I was 18) I started weight training, mostly low impact isometric exercises, dumbells and stretch bands.
I now feel better than I have in 30 years. If I could do it, anyone can.
Movie Bruce Almighty.
Woman: I’m just so thrilled on my Krispy Kreme diet. I’m losing pounds every week.
“And the side effects are.....???”
You’d probably feel very active. I’m sure it’s a stimulant.
What about the set point?
A person’s body tries to maintain equilibrium for food intake and weight maintenance. Homeostasis.
Take away certain foods and you lose a little weight-—but the body says “okay, that’s the new amount to keep from losing more weight.” Again and again.
In the PBS special and book The Truth About Fat they interviewed the Biggest Loser stars three years later and all of them were really obese again.
https://www.ncbi.nlm.nih.gov/books/NBK592402/
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.