A scanning electron micrograph of a section through a vein in the liver, showing red blood cells surrounded by hepatocytes (green). (CREDIT: PNAS Nexus) Posted on 12/12/2024 11:26:21 AM PST by Red Badger
The importance of this technique becomes even clearer when considering the larger context. An astonishing 100 million Americans are affected by obesity and related cardiometabolic disorders, notes S. Thai Thayumanavan, a distinguished biomedical engineer and chemist at the University of Massachusetts Amherst. "We were really excited about this work," he says.
The brilliance of this method lies in the nanogel itself. These tiny carriers are packed with a synthetic thyroid hormone drug called a thyromimetic. While thyroid hormones are crucial for liver metabolism, they often prove ineffective and cause adverse side effects when taken systemically.
"We came up with a very simple approach, using our unique invention – nanogels that we can direct selectively to different targets," Thayumanavan continues, underscoring the customized nature of their method. "They were custom-designed for hepatocyte delivery in the liver."
The outcomes were nothing short of remarkable. "The treated mice completely lost their gained weight, and we did not see any untoward side effects," reports Thayumanavan.
A scanning electron micrograph of a section through a vein in the liver, showing red blood cells surrounded by hepatocytes (green). (CREDIT: PNAS Nexus)
Yet, it wasn't just about shedding weight. The mice, who continued their rich diets, saw normalized cholesterol levels and a significant reduction in liver inflammation. "We found that we are activating the reverse cholesterol transport pathway, which lowers cholesterol," Thayumanavan elaborates.
He further theorizes, "We believe that activation of fat oxidation and an increase in metabolic rate are causing the loss in weight, but more work needs to be done to prove that point."
Delving into the mechanics, once these nanogels permeate the hepatocytes, the liver cell environment disintegrates the bonds within the nanogel, releasing axitirome. This drug subsequently latches onto proteins pivotal for gene expression regulation.
The apparent effectiveness of the ANG-delivered axitirome, which reversed weight gain without disrupting thyroid hormone levels, indicates a promising avenue for thyromimetics in addressing metabolic diseases like obesity.
An interesting observation emerged: mice on axitirome retained their appetite for high-calorie food. This is in stark contrast to human subjects using other weight loss drugs.
"There is a significant amount of development work to be conducted between mice and humans," Thayumanavan cautions, "but we are hoping it will eventually become a drug."
Driven by the promise of the nanogel technology his lab birthed, Thayumanavan has launched a startup, Cyta Therapeutics. Their primary mission? To spearhead cutting-edge delivery platforms ensuring drugs are dispatched to their intended bodily destinations.
The exciting potential of this discovery cannot be understated. It not only offers a beacon of hope for those grappling with obesity and associated disorders but also paves the way for further advancements in drug delivery, potentially revolutionizing the treatment of metabolic diseases.
Other health benefits of thyromimetic drugs
Thyromimetic drugs mimic the action of thyroid hormones, and their health benefits extend beyond traditional thyroid hormone replacement therapies. These drugs can have a range of effects due to their influence on metabolism, cardiovascular function, and lipid regulation. Here are other potential health benefits of thyromimetic drugs:
Cardiovascular Health
Improvement of Lipid Profiles: Thyromimetic drugs can reduce levels of low-density lipoprotein (LDL) cholesterol and triglycerides while increasing high-density lipoprotein (HDL) cholesterol. This makes them promising in managing dyslipidemia and reducing cardiovascular risk.
Reduced Atherosclerosis Risk: By improving lipid profiles and reducing arterial inflammation, thyromimetics may help prevent or slow the progression of atherosclerosis.
Weight Management and Metabolism
Increased Energy Expenditure: These drugs can stimulate metabolic pathways, potentially aiding in weight management and combating obesity by increasing basal metabolic rate.
Fat Reduction: Some thyromimetics selectively target tissues to enhance lipolysis and reduce fat stores without significant effects on the heart or skeletal muscle.
Liver Health
Non-Alcoholic Fatty Liver Disease (NAFLD): Thyromimetic drugs, particularly those targeting thyroid hormone receptor beta (TRβ), have shown promise in reducing liver fat content, improving liver function, and addressing NAFLD and non-alcoholic steatohepatitis (NASH).
Bone and Muscular Health
Bone Health: Thyromimetics may enhance bone remodeling by influencing osteoblast and osteoclast activity, which can be beneficial in treating conditions like osteoporosis.
Muscle Strength and Function: By optimizing metabolism, thyromimetics may improve muscle energy efficiency and strength.
Neurological and Cognitive Function
Neuroprotection: Thyroid hormones are critical for brain development and function. Thyromimetics might support neural regeneration and cognitive function, particularly in neurodegenerative diseases.
Mood Regulation: Thyroid hormone modulation has been linked to improved mood and mental health, potentially addressing symptoms of depression in some patients.
Improved Glucose Metabolism
Enhanced Insulin Sensitivity: Thyromimetics can improve glucose metabolism, which may benefit individuals with type 2 diabetes or insulin resistance.
Anti-Inflammatory Effects
Systemic Inflammation Reduction: These drugs may help reduce inflammation markers, contributing to overall health improvements in conditions associated with chronic inflammation.
Potential Anti-Aging Properties
Cellular Metabolism Support: By stimulating mitochondrial activity and cellular energy production, thyromimetics may have anti-aging benefits, supporting cellular repair and longevity.
Ongoing Research
Researchers are investigating the selective activation of thyroid hormone receptors (TRα and TRβ) to maximize these benefits while minimizing side effects, such as cardiac risks. Targeting TRβ, for example, is particularly promising in lipid metabolism and liver disease without significant effects on the heart.
While these additional benefits are promising, it is important for patients to use thyromimetic drugs under medical supervision to avoid side effects or interactions with other medications. Each patient's overall health condition determines which drugs will provide the most comprehensive benefits.
I’m in. I’m overweight, have diabetes, low energy and depression, and my memory is getting bad. At my age (73), I’ll take all the help I can get. What??? You say its $1500 a month??? Not covered by Medicare??? Aw, nuts!
Easy solutions are appealing.
Movie Bruce Almighty (2003):
Happy woman:
“l lost 47 pounds on the Krispy Kreme diet.”
🍩🍩🍩🍩🍩🍩🍩🍩
Is some of this breakthrough stuff happening because of AI?
“I’m in. I’m overweight, have diabetes, low energy and depression, and my memory is getting bad. At my age (73), I’ll take all the help I can get.”
Self-righteous FReepers have zero empathy for you.
I know. I just don’t care what they think.
It seems that all we need is better health and nutrition information — so people don’t become obese and diabetic in the first place. For most people, that would simply be knowing that they don’t have to be eating and drinking every five minutes — or their bodies will die of starvation and thirst. Most of the problems of contemporary life is the problem of excessive indulgence — rather than the lack of the latest pharmaceutical invention.
We have to go in the direction of less — and not more — and eliminate the fat and excess in our society. That’s what the Department of Government Efficiency (DOGE) should be leading the way. We can do more with less — which is the sign of intelligence — rather than winning Nobel prizes for enabling these problems.
That’s the Trump era. More health and not simply more health care.
Hubby is a Type 2. Was 50 pounds overweight.
He lost the weight, kept it off. Has been able to drop some of his meds. His bloodwork is excellent.
You know how he does it?
The hard way.
It works.
Eat as much of whatever I like.
No change in diet or appetite.
No need, or even mention of, exercise.
And I lose weight AND lower my cholesterol?
This one is right up there with the 200 mpg carburetor and perpetual motion machine.
“There is a significant amount of development work to be conducted between mice and humans,” Thayumanavan cautions, “but we are hoping it will eventually become a drug.”
—
Someday, in the far far future it will be a pill, not an injection.
It works for everyone except those for whom it doesn’t work - and not everyone for whom it doesn’t work is a slovenly, inferior human being - as is frequently the implication hereon.
“Jabba was Star Wars, not Star Trek.”
Ah! That explains it then. Star Wars happened a long time ago, not in the future like Star Trek.
I don’t think so ...for now................
Which folks would those be...?
Another wonder drug. A long article with a lot of terminology that no one understands. I wonder what the long term effects are. Like every other wonder drug the hype will not be realized. Apparently this sort of psyop is eternally effective.
I’d bet that banning high fructose corn syrup would do more good. Child obesity rates increased drastically when the corn shyt was introduced.
Ditto. Losing weight becomes problematic when you have to balance it with your blood sugar level. Eat too little and BS plummets, sometimes to dangerous levels. I’ve had days when I’ve had to eat way too much to get my BS up to a safe range. Likewise, days when I’ve eaten nothing and my BS still went higher.
Polymer based nanogels.
**************************************
Kind of sounds like glue that might be used to glue your mouth shut.
Ultra processed and hyperpalatable foods increased dramatically when tobacco giants starting acquiring food companies (Kraft, Nabisco, General Foods, Cheez-Whiz etc) from the ‘80’s-2000. They had to walk away when Big Food litigation became too much like Big Tobacco.
It is probably going to be a many pronged strategy but banning some of the ingredients would be a start, especially for children that aren’t able to benefit from drugs and those that need vanity weight loss not approved for use by the FDA.
I weigh 112 and hate the idea of torturing any animal, especially lab animals.
Bull fighting sux too.
A good diet includes fruits, veggies, mostly organic, and avoidance of pork and beef. Pasture-raised chicken and eggs are fine with me. Alaskan salmon too.
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