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A New Generation of Weight-Loss Drugs Target Brain Plasticity

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A breakthrough in weight-loss drug development is on the horizon, thanks to the innovative research led by Associate Professor Christoffer Clemmensen from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen. Clemmensen and his team have developed a new type of weight-loss drug that affects brain plasticity and shows promising results in preclinical studies. Published in the scientific journal Nature, this new drug could potentially offer a more effective and targeted approach to weight loss.

The Role of GLP-1 in Weight Loss

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In their study, the researchers demonstrate a novel use of the weight-loss hormone GLP-1. Traditionally, GLP-1 has been used to help manage weight, but Clemmensen’s team discovered that it could serve as a ‘Trojan Horse’ to deliver specific molecules into the brain. These molecules target the brain’s plasticity, resulting in significant weight loss in mice.

The study suggests future patients could achieve similar weight-loss results with lower doses, potentially reducing side effects.

From Mice to Humans: The Next Steps

Currently, the new drug is in the preclinical phase, involving studies on cells and experimental animals. The next critical step is to conduct clinical trials with human participants. These trials will determine how the drug works in humans and whether the impressive results seen in mice can be replicated.

Clemmensen is optimistic about the potential of this drug, noting that GLP-1-based drugs are already known to induce weight loss. By attaching a molecule that affects the glutamatergic neurotransmitter system to GLP-1, the team has created a drug that may offer significant weight loss benefits. Previous studies with similar compounds have shown promise in human participants, further supporting the potential of this new drug.

Overcoming the Brain’s Defense Mechanisms

The human body is naturally designed to defend a certain body weight and fat mass, a trait that has historically helped humans survive periods of food scarcity. However, in today’s world, where obesity is a growing problem, this evolutionary advantage can be detrimental.

Clemmensen and his team developed an interest in molecules used to treat chronic depression and Alzheimer’s disease, which block a receptor protein called the NMDA receptor. These receptors play a key role in brain plasticity, affecting long-term changes in brain connections. By targeting these receptors, the new drug can potentially alter the brain’s structure and function to promote weight loss.

The Potential of Targeted Drug Delivery

A significant innovation of this new drug is its targeted delivery method. By combining GLP-1 with molecules that block the NMDA receptor, the drug specifically targets the neurons that control appetite. This specificity reduces the risk of non-specific effects that can cause severe side effects, a common issue with many neurobiological drugs.

“This family of molecules can have a permanent effect on the brain,” Clemmensen explains. “We see molecular signatures of neuroplasticity in our work, but in this case, in the context of weight loss.” The drug’s ability to cross the blood-brain barrier and target specific brain regions marks a significant advancement in weight-loss treatment.

Implications for Future Treatments

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The implications of this research extend beyond weight loss. By using GLP-1 as a vehicle to deliver drugs to specific parts of the brain, Clemmensen’s team has opened the door to a new class of treatments for various neurodegenerative diseases and psychiatric disorders. This approach could lead to more effective and targeted therapies for conditions that have been difficult to treat due to the challenges of crossing the blood-brain barrier.

Understanding Neuroplasticity

Neuroplasticity, or the brain’s ability to restructure itself by forming new neural connections, is central to this new drug’s mechanism. This ability allows the brain to adjust to new experiences, learn new skills, and recover from injuries. By harnessing neuroplasticity, the new drug can potentially bring about long-lasting changes in brain function that promote weight loss.

In conclusion, the development of this new weight-loss drug represents a significant step forward in the fight against obesity. By targeting brain plasticity and utilizing innovative drug delivery methods, Clemmensen and his team have created a promising new treatment that could benefit millions of people struggling with weight management. As research progresses and clinical trials begin, the potential for this drug to revolutionize weight-loss therapy becomes increasingly clear.

Are you excited about the brain side effects of weight loss drugs? Leave your thoughts in the comments below. 

 

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Fitness

Say Goodbye to BMI: Here’s the New Metric For Measuring Healthy Weight

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For decades, Body Mass Index (BMI) has been the go-to method for estimating a person’s body fat and categorizing their weight status. However, new research suggests that BMI might not be the best tool for this job. A study published in JAMA Network Open introduces the Body Roundness Index (BRI) as a more precise alternative.

The Limitations of BMI

BMI, developed in 1832, has been widely used since the 1980s. Despite its popularity, BMI has significant limitations. It calculates body fat based on height and weight alone, without considering other crucial factors like muscle mass, bone density, and fat distribution. This means BMI can misclassify individuals with different body compositions. For example, athletes with high muscle mass often have a higher BMI, which inaccurately suggests they have excess body fat. Conversely, older adults with less muscle mass might have a lower BMI, overlooking excess fat.

What is the Body Roundness Index?

The BRI aims to address these shortcomings by incorporating additional measurements. Unlike BMI, which only uses height and weight, BRI also considers hip and waist circumferences. These extra measurements help estimate total body fat and visceral fat more accurately. Visceral fat, a deep belly fat surrounding the organs, is particularly harmful to health.

How BRI Works

BRI is based on the concept that the human body is more egg-shaped than cylindrical. By comparing waist or hip circumference to height, BRI provides a more nuanced picture of body composition. Developed by Diana Thomas, a mathematics professor at the U.S. Military Academy at West Point, BRI uses the mathematical concept of eccentricity. Essentially, the closer someone is to being circle-shaped, the closer their BRI will be to zero. Conversely, the more they resemble a straight line, the closer their BRI will be to one.

Why BRI is More Accurate

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The study analyzed data from the National Health and Nutrition Examination Survey, involving around 33,000 Americans over nearly 20 years. Researchers found that BRI was better at categorizing individuals’ weight status and estimating their body composition. When plotting the risk of death based on BRI, the data formed a bell curve, clearly showing higher risks at both extremes. BMI data, on the other hand, produced a flatter curve, masking important variations in the middle range.

Practical Benefits of BRI

One of the main advantages of BRI is its accessibility. Unlike specialized scales or scans, which are not always available or accurate, BRI only requires a measuring tape. This simplicity makes it easier for more people to use, promoting better health tracking across various settings.

While BRI is a significant improvement over BMI, it’s not without its own limitations. It still doesn’t measure muscle mass, which is a crucial component of overall health. However, experts believe BRI is a step in the right direction toward more accurately measuring body composition.

As we learn more about the complexities of body composition, it’s clear that BMI is not a one-size-fits-all measure. The Body Roundness Index offers a more accurate and accessible way to assess obesity and related health risks. Have you ever measured your BRI or used another method to understand your body composition? Share your experiences and thoughts in the comments below!

 

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Fitness

Overweight and Obesity in Youth Linked to Increased Stroke Risk in Women

A comprehensive analysis of over 50 years of health data has revealed a significant correlation between being overweight or obese at a young age and the risk of experiencing an ischemic (clot-caused) stroke before the age of 55 in women. This research, published in Stroke, the journal of the American Stroke Association, highlights the long-term health impacts of early life weight issues.

The study, conducted in Finland, examined the influence of body weight at ages 14 and 31 on stroke risk. It found female participants who were overweight by 14 had significantly increased chances of strokes later in life –  even if they lost the weight by 31. Similarly, women who were overweight at age 31 had a higher risk of stroke regardless of their weight at age 14. Notably, this increased risk was not observed in men who were overweight at ages 14 or 31. However, men with obesity at age 31 showed a higher risk of bleeding stroke compared to women with obesity at the same age.

Long-term Health Effects of Early Weight Issues

Long-term Health Effects of Early Weight Issues

Lead study author Ursula Mikkola, B.M., from the Research Unit of Population Health at the University of Oulu, emphasized the long-term health effects of being overweight, even if the excess weight is temporary. She advocates for healthcare professionals to address overweight and obesity in young people by promoting healthier eating patterns and physical activity, but to do so in a non-judgmental and non-stigmatizing manner.

Data from the Northern Finland Birth Cohort 1966

Data from the Northern Finland Birth Cohort 1966

The researchers utilized data from the Northern Finland Birth Cohort 1966, which has followed more than 10,000 individuals from birth into their 50s. This extensive dataset allowed for a thorough analysis of the impact of body mass index (BMI) at different ages on the risk of early stroke.

The study found that approximately 1 in 20 participants experienced a clot-caused stroke or transient ischemic attack (TIA) during the follow-up period. Women with obesity at age 14 were 87% more likely to experience a clot-caused stroke, and those with obesity at age 31 were 167% more likely to have a stroke compared to their peers at appropriate weight. Women with obesity at age 31 also had nearly 3 ½ times the risk of bleeding stroke, while men with obesity at the same age had more than 5 ½ times the risk of bleeding stroke.

Implications for Preventive Health

Implications for Preventive Health

The findings suggest that addressing weight issues early in life can have a significant impact on reducing stroke risk later on. Mikkola advises that adopting a healthy lifestyle, including balanced eating, regular physical activity, avoiding smoking, and managing other health parameters like blood pressure and cholesterol, can help mitigate the risk of stroke even if one was overweight during youth.

The study found that the increased risk of clot-caused stroke was specific to women, with researchers currently investigating the underlying reasons for this gender disparity. This research will help to better understand the complex interactions between gender, weight, and stroke risk.

Editorial Insights

Editorial Insights

In an accompanying editorial, Dr. Larry Goldstein, a member of the American Heart Association Stroke Council, noted the significance of these findings. He highlighted that while the data supports the association between early-life overweight/obesity and stroke risk, further research is needed to determine if reducing overweight/obesity in younger populations will lead to lower stroke rates in adults.

The analysis included 10,491 participants in their 50s, with BMI measured at ages 14 and 31. The study identified ischemic strokes and TIAs using national hospital and death registers and adjusted for various factors, including smoking status, education levels, and age at first menstrual period for women.

However, as an observational study, it cannot definitively establish a cause-and-effect relationship between weight and early stroke risk. Additionally, the study’s population was exclusively Finnish, which may limit the generalizability of the results to other populations.

This study underscores the critical importance of early weight management and healthy lifestyle choices in reducing the risk of stroke later in life. Addressing obesity and overweight issues during youth can have profound long-term health benefits, particularly for women.

What steps have you taken to manage your weight and reduce health risks? How do you think these findings should influence public health strategies? Share your thoughts and experiences in the comments below. Your insights could help others take proactive steps towards a healthier future.

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Overweight? Here’s WHEN You Should Exercise

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Recent research from Spain suggests that exercising in the evening can be particularly beneficial for managing blood sugar levels in people who are overweight or obese. This study underscores the importance of precision in exercise prescription, highlighting that the timing of physical activity can significantly impact its effectiveness.

Conducted by a team led by Jonatan R. Ruiz, a professor of physical activity and health at the University of Granada, the research tracked the blood sugar levels and physical activity patterns of 186 overweight or obese adults. Participants were divided based on their exercise times: between 6 a.m. and noon, noon to 6 p.m., or 6 p.m. to midnight.

The results were striking. Those who exercised in the evening exhibited lower blood sugar levels throughout the day, at night, and overall, compared to those who exercised earlier in the day. This effect was even more pronounced in participants with prediabetes, a condition that significantly increases the risk of developing Type 2 diabetes.

The Importance of Timing in Exercise

Study author Jonatan R. Ruiz emphasized that certified sports and medical professionals should consider the optimal timing of exercise to enhance the effectiveness of the physical activity programs they prescribe.

The findings, to be published later this year in Obesity, the flagship journal of the Obesity Society, contribute to a growing body of evidence suggesting that the timing of exercise can influence metabolic outcomes. For instance, a UK study released in April found that nighttime physical activity could lead to lower morning blood sugar levels. Additionally, research from May 2023 indicated that adults with Type 2 diabetes saw the best blood sugar control when they were most active between 1:43 p.m. and 5 p.m.

Why Evening Exercise?

The reasons why evening exercise may be particularly effective for blood sugar management are not yet fully understood. However, it is hypothesized that exercising later in the day may better align with the body’s circadian rhythms, which regulate many physiological processes, including metabolism.

Additionally, post-meal exercise is known to help manage blood sugar spikes. Given that many people consume their largest meal in the evening, engaging in physical activity afterward could help mitigate these spikes and improve overall blood sugar control.

Practical Implications

Dr. Lucy Chambers, head of research communications at Diabetes UK, commented on these findings, noting that while afternoon exercise appears to offer significant benefits, the most crucial factor is consistency. This could be before work, during a lunch break, or in the evening.

For individuals with Type 2 diabetes or those at risk, incorporating evening exercise into their daily routine could be a strategic way to manage blood sugar levels. Activities such as brisk walking, jogging, cycling, or even engaging in a group fitness class can be effective.

Broader Context

With over 38 million Americans living with diabetes, characterized by elevated blood sugar levels, finding effective management strategies is crucial. Alongside dietary modifications and medications, exercise is a cornerstone of diabetes management. This new research provides an additional layer of nuance, suggesting that not only the amount and type of exercise but also the timing can make a significant difference.

In summary, evening exercise could offer a strategic advantage for blood sugar management in overweight and obese individuals. While further research is needed to fully understand the mechanisms behind this effect, the current findings support the inclusion of evening workouts as part of a comprehensive approach to managing blood sugar levels and overall metabolic health.

Have you tried adjusting the timing of your exercise routine to see if it affects your blood sugar levels? What strategies have worked best for you? Share your experiences and insights in the comments below. Your contributions could help others find effective ways to manage their health through exercise.

 

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