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 think it’s a combo of weight loss and short time.
However, I think there might be interesting results if further combined with wrinkle reducing Botox injections.
50+ years ago obesity was rare. It was only when we started to rely on foods whose labels require a degree in organic chemistry to understand that we began to see this problem.
#3 Jabba was in Star Wars and he was the skinny one of his species as he was taking the new drug...
BTW that is a cool photo of red blood cells surrounded by hepatocytes (green)
XD...
Look Phil, we all saw the movie... it clearly said it happened a long time ago and a long way away!
That fat sack of crap. I figured as much.
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