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.
From whose perspective? Their long time ago could be the remains of a vanished future.
A muzzle seems more appropriate attire now.
RE: William Shatner....
On the kids’ show Max Headroom they had the guest star William Shatner talk to the simulated host on his TV screen.
Shatner: “I think they should take all the money that funds the Defense Department and give it all to the Department of Education.”
Imaginary host cheered and said “wow” over and over.
Those kids are probably the CEO shooter’s age now. Or actually older (so in Congress).
The imaginary future of Star Trek....
A coworker in the 1970s said her girlfriend had a beach towel for the show that said:
“Where No Man
Has Gone Before.”
She and her friends laughed.
“Yeah, sure, I’ll bet.”
My diet exactly. Except for chicken or eggs. And at least there is hope now for the FDA to comply with applicable law. To stop signaling to drug developers that extensive animal testing is required when it is not because they refuse to modernize the efforts of the agency and to accept new, better, life-saving science.
“Except Jabba, not sure what his deal was.”
Jabba received government cheese and food stamps
There are various metabolic disorders that affect how people respond to dietary changes, as well as physical conditions (musculoskeletal, neurological/balance, etc) that affect their ability to exercise. Mental disorders can also affect adherence to dietary/exercise protocols.
“The hard way” is preferable but it’s not a universal antidote.
True.
Another show I saw then (nephews’ viewing these) had some animated kids (asian, black, assertive girl, helpful but mostly passive white male in the background) tracking what turned out to be a deliberate polluter CEO secretly ordering dumping industrial liquid waste into the river.
He was white, quite heavy, around age 60, totally bald on top and wore a fancy suit and tie. Looked like Rush Limbaugh, Karl Rove and especially Roger Ailes.
The kids brought him to justice and saved the day.
Those kids now the shooter’s age or older.
No Scooby snacks? /sarcasm
Genetics and metabolism didn’t permanently alter over the last 30 years. Obesity is not a disease Americans have no control over regardless of what Oprah claims. It is going to be a gradual process (exercise as a standard prescription while drugs are phased out in some cases) with many specialized components but giving everyone Ozempic and doing nothing else is not the answer either.
Eat less
“Genetics and metabolism didn’t permanently alter over the last 30 years.”
I didn’t say they had.
“Obesity is not a disease Americans have no control over regardless of what Oprah claims.”
I didn’t say it was.
“It is going to be a gradual process (exercise as a standard prescription while drugs are phased out in some cases) with many specialized components”
For many, but not for everyone.
“...giving everyone Ozempic and doing nothing else is not the answer either.”
I didn’t say it was.
That is Trump’s goal as well. lol Right ? He has tasked RFK Jr with the goal of concrete reductions in chronic disease in children in two years. Kids don’t have control what they are fed at home, presuming a family that can even afford healthy low fat food. So there needs to be a mandated effort to ban some of these more harmful ingredients.
I’ll let the hollyweird people be the guinea pigs.
Yep, removing fat from under the skin will cause the skin to wrinkle. Doesn’t matter if it Ozempic, a gastric bypass, or just losing weight: the fat stretched out the skin and when the fat is gone, the skin will wrinkle.
I recently lost 30lbd. I did it the old fashion way, diet and exercise. I need to lose more and I’m struggling. But no way in heck and I’m going to take a med to do it.
ANd it only cost you $8k per month.
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