Posted on 09/06/2026 4:53:53 PM PDT by nickcarraway
A compound called TOFA helped obese mice lose 18% of their body weight without eating less, while preserving lean tissue and improving blood sugar and liver fat.
Medicines such as semaglutide and tirzepatide have changed how doctors treat obesity and type 2 diabetes.
They copy signals from gut hormones, including GLP-1, that reduce hunger.
These drugs can help people lose weight, but they can also cause nausea and other digestive problems.
Some people may lose lean tissue, including muscle, which could create health problems over time.
Obesity often appears with high blood sugar and excess liver fat.
Researchers at the University of California, Berkeley (UC Berkeley) tested another approach in mice using a compound called 5-tetradecyloxy-2-furoic acid, or TOFA.
A different treatment route TOFA was first identified decades ago. It blocks ACC1 and ACC2, two enzymes that help cells make fatty acids and control whether the body stores or burns fat.
Other compounds that block these enzymes can lower liver fat, but many also raise triglycerides. These fats travel in the blood and can become harmful at high levels.
Senior author Professor Anders Näär described body weight as the result of two basic forces.
“Body weight responds to two levers: taking in fewer calories, or spending more energy,” Professor Näär said.
“GLP-1s work almost entirely on the first, so we went after the second.”
Testing TOFA in mice In one main experiment, male mice ate a high-fat diet for seven weeks.
The team then gave TOFA to 10 mice by mouth for four weeks, while another 10 mice received only the liquid carrying it.
The TOFA-treated mice lost an average of 18% of their body weight. They did not eat less, and most of the lost weight came from fat rather than lean tissue.
TOFA also lowered fasting blood sugar and insulin. Insulin is a hormone that helps cells take glucose from the blood and use it for energy.
The mice handled an injected dose of glucose more effectively. Their liver fat, blood triglycerides, and cholesterol levels also fell.
Mice used more energy The team placed another group of obese mice in special cages. The cages measured food intake, movement, oxygen use, carbon dioxide production, body temperature, and total energy use.
After allowing for differences in body size, the TOFA-treated mice used about 18% more energy at 73°F (23°C) and 86°F (30°C). They did not move more, and their body temperatures did not rise.
The animals also did not lose extra calories through their waste.
The increase was much smaller in the cold, suggesting that ordinary heat-producing fat tissue could not fully explain it.
Liver cells from treated mice used more oxygen. This pointed to greater activity in mitochondria, structures inside cells that turn nutrients into usable energy, with fat as the main fuel.
One compound, two actions TOFA did more than block ACC1 and ACC2. It also turned on PPAR-alpha and PPAR-delta, two proteins that control genes involved in burning fat and managing energy.
The team found that TOFA interacted directly with both proteins. Separate drugs that blocked ACC enzymes and activated PPAR proteins did not produce the same overall results.
First author Justin Y. Lee described this combined effect. “TOFA appears to engage a coordinated metabolic response,” Lee said.
“It is not simply blocking lipid synthesis. It is also activating energy expenditure pathways that may help the body handle excess lipid and glucose more effectively.”
Fatty liver signs improved
The researchers also tested TOFA in two mouse models of serious fatty liver disease.
This condition starts when too much fat collects in the liver and can lead to inflammation, cell damage, and scarring called fibrosis.
In the first model, four weeks of treatment reduced liver fat. It also lowered the activity of genes linked to inflammation and scarring, along with a sign of harmful chemical stress.
Liver samples showed less fat and fibrosis. However, two common blood markers of liver damage did not show a reliable difference between the groups.
The second model involved more advanced liver damage.
After six weeks, treated mice had less liver fat, lower triglycerides, less fibrosis, and lower activity in many inflammatory signals.
Combining the two approaches
The team then tested TOFA with semaglutide or tirzepatide.
Small groups of obese mice received one treatment alone or a combination for 24 days, and the combinations caused more weight loss than any single treatment.
The extra loss came from fat, while lean mass did not clearly fall. Blood sugar control, fasting insulin, and triglyceride levels generally improved most in the combination groups.
“In our combination experiments, TOFA worked additively or synergistically with the GLP-1 appetite-suppressing drugs, so we view it as complementary rather than as a replacement,” Professor Näär said.
In another experiment, mice given TOFA kept their lower weight longer after treatment ended than mice given semaglutide.
Each group had only five animals, so the result does not show that people would respond in the same way.
Human safety still needs testing
All animal experiments used male mice. The results may differ in female mice, and several important tests included only four to 10 animals in each group.
Most treatments lasted only a few weeks. The experiments cannot show how TOFA might affect the body after months or years of use.
TOFA has not been tested in people. Researchers still need to find its safest dose, its lowest effective dose, and any possible long-term or less obvious harms.
Not every result was clear. One broad test of the body’s response to insulin did not show a reliable difference, and other tissues or proteins may also contribute to TOFA’s effects.
What the findings mean
TOFA points to a different possible way to treat obesity and related health problems.
Instead of working mainly by reducing hunger, it may help the body use more energy while improving how it handles fat and glucose.
The mouse results also suggest that TOFA could work beside GLP-1 drugs rather than replace them. Human trials must test whether the benefits remain and whether the treatment is safe.
For now, TOFA is only a candidate for more animal testing and carefully controlled human trials. Doctors cannot yet give it to patients.
The study is published in the journal Science Advances.
Dear FRiends,
We need your continuing support to keep FR funded. Your donations are our sole source of funding. No sugar daddies, no advertisers, no paid memberships, no commercial sales, no gimmicks, no tax subsidies. No spam, no pop-ups, no ad trackers.
If you enjoy using FR and agree it's a worthwhile endeavor, please consider making a contribution today:
Click here: to donate by Credit Card
Or here: to donate by PayPal
Or by mail to: Free Republic, LLC - PO Box 9771 - Fresno, CA 93794
Thank you very much and God bless you,
Jim
Do you know what is really good for breakfast?
Good coffee, a few slices of bacon just as you like it, a half a piece of toast, and a perfect banana split.
Why can’t people just eat less, eat less food, get on a basic exert routine.
I took care of old people my whole career. The ones who make it into their 90s were thin, or fit, didn’t depend on pharmaceutical
Had discipline.
A lot of people can go on diets and exercise and still not lose weight.
“ A lot of people can go on diets and exercise and still not lose weight.”
If they set their sights on eating real food three meals a day balanced. Very little added sugar very little alcohol and move regularly daily with an exercise routine and they do this for a couple of years with no intention of going back to regular beer and chips, candy, overeating, packaged processed food, I can’t see anyone not losing weight
They just want to go back to their high school diet, eating and drinking at night, drinking soda, eating cookies regularly and they want to lose weight in a few weeks, again, like high school
They angrily go on ozempic then they look like crap. Who knows how it affects longevity
I am not a nutritionist. I have consulted nutritionists. Here’s what they say. Eat right. Read labels. Don’t eat non food. Lose weight slowly 5 pounds per month or so equals two years for real weight loss when people are way over weight
“Why can’t people just eat less, eat less food, get on a basic exert routine.”
That’s what my grandmother did every day when she was middle-aged. She went to the gym and worked out. Or sometimes went on long bicycle rides. She said virtually all of the housewives worked out and took long bicycle rides, which is why her generation had neither an obesity problem nor a diabetes problem. But then starting in the late 1980s (more my mom’s generation at that point) the housewives just stopped, all at once, simply refused to do all that extra exercise...and thus got fat and sick, but still never gave a thought to going back to all that daily exercise - they just simply REFUSE! So it’s their fault.
“A lot of people can go on diets and exercise and still not lose weight.”
Don’t be a party pooper, we need to keep the focus on the people getting sick, otherwise we might start asking questions as to what has changed in our food supply, particularly the type of wheat we grow. We don’t to go there, far too many jobs at risk - particularly in the medical and food industries.
So, like I said in my prior post, it’s the fault of the fat and sick, AND THAT’S FINAL!!!
The processing of food has to be counteracted
The way wheat is processed is part of it. Gluten intolerance?
Where did that emerge?
Eating real food is key I am told.
“The way wheat is processed is part of it. Gluten intolerance? Where did that emerge?”
Actually, it’s the genetic makeup of the Wheat. In the 1950s, by Norman Borlaug. Here’s Google’s summary:
“Norman Borlaug developed semi-dwarf, high-yield, disease-resistant wheat varieties that sparked the Green Revolution and saved over a billion people from starvation”
He did this by hybridizing wheat (as opposed to gene splicing, which wasn’t around back then), which increased per-acre yields by 3 to 4 times. But unlike the old form of wheat, which humans had 10,000 years or so to adapt to, humans are not even close to fully adapting to Borlaug’s wheat, and so some people haven’t adapted at all are Gluten Intolerant, while MOST PEOPLE can eat his wheat, but their bodies do not yet have an efficient way to process it, so it’s immediately turned into glucose (blood sugar), which drives up insulin production, which causes insulin resistance, which directly leads to both obesity and diabetes, which then leads to trillions for Big Food, Big Pharma, and Big Medical (while making life miserable for many millions of adults, but who cares, it’s the money that counts!).
That’s what we’re eating. A lot of nonsense
“That’s what we’re eating.”
Exactly.
There's a lot of evidence you are right. Elderly grossly overweight people are rare--probably for a lot of good reasons.
Zig Ziglar used to advise people to ask their slender doctor for weight loss advice. And if their doctor is actually fat, get a new doctor fast.
His doctor said in his office: "With my diet you will be happy to learn you can eat everything you want." Then he pulled out a sheet from his desk. "This is a list of everything you're going to want to eat."
Then there are also those phyto-estrogen containing seed oils that Ancel Keyes pushed to replace healthy animal fats like butter!
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.