5-Amino-1MQ

5-Amino-1MQ: An Introduction

The compound 5-amino-1methylquinolinium (5-amino-1MQ) is a small analogue of methylquinolinium that functions as a selective peptide-based inhibitor of the enzyme nicotinamide N-methyltransferase (NNMT) found in the cytosol. Scientific research has established connections between NNMT enzyme activity and metabolic disorders including obesity and type 2 diabetes, with this enzyme serving a critical role in cellular energy balance. Blocking NNMT activity results in remarkable weight loss, reduced fat mass and smaller fat cell dimensions, plus improved cholesterol and glucose measurements in blood plasma. Currently, 5-amino-1MQ and related methylquinolinium compounds are being studied as promising therapeutic options for managing weight and diabetes. Evidence also suggests that NNMT inhibition may activate stem cells and enhance regenerative function in skeletal muscle tissue.

5-Amino-1MQ Molecular Structure

Molecular Formula: C₁₀H₁₁N₂
Molecular Weight: 159.21 g/mol

Source: pubchem

5-Amino-1MQ Research Studies

Obesity Applications

We currently face a worldwide health challenge with obesity, a condition initially common in wealthy nations but now prevalent globally in both men and women. Research demonstrates that elevated NNMT levels are associated with metabolic problems. This enzyme has been connected to lipid storage and diabetes progression. In rodent studies, mice that produce high GLUT4 levels are thinner, healthier, and demonstrate improved insulin response. Conversely, mice exhibiting diabetes with high fat content and low GLUT4 levels demonstrated profound insulin resistance.

Studies on mice show that excess body weight is caused by metabolic imbalance and unusually high NNMT enzyme levels, leading to moderate weight gain. This increase stimulates NAD+ (Nicotinamide Adenine Dinucleotide), decreasing the requirement for GLUT4. As GLUT4 levels drop, insulin resistance develops, accelerating weight accumulation and obesity. Studies reported that in test subjects displaying weight accumulation, inhibiting NNMT shows promise for treatment and weight control. Research indicates that treatment of diabetic and obese mice with low GLUT4 levels demonstrates improved conditions, including in animals with natural resistance. Manipulating this pathway has shown progress in managing obesity and insulin resistance, and thus diabetes. In one study, overweight rodents exposed to NNMT inhibitory compounds exhibited all features of metabolic excellence. Human metabolism normally operates with high efficiency. Unfortunately, this very efficiency may work against efforts to reduce weight gain, making interventions more challenging when caloric intake is excessive. Understanding the genetic and molecular mechanisms underlying our propensity for obesity in the setting of excess calorie intake will likely reveal additional causes. Decreasing NNMT due to its relationship with GLUT4 may be the link that scientists have been searching for.

In basic terms, NNMT determines how rapidly the body absorbs calories, making them available for storage in fat or glycogen. Decreased NNMT increases inhibition of this enzyme, leading to SAM (S-adenosyl methionine) being used in alternative pathways. This has two metabolic effects:

[DIAGRAM: Metabolic pathway showing NAD+, NNMT, SAM interactions and their effects on fat storage and insulin]

Source: Science Brief

The net result of administering an NNMT blocker like 5-amino-1MQ is an increase in metabolic efficiency with a decrease in energy storage. When this is coupled with SAM's role in cellular processes, this provides another excellent reason for improvements in glucose and blood markers. Research also discovered potential benefits to liver function and energy levels. In rat studies, white adipose tissue (WAT) decreased by approximately 3%, while cholesterol decreased by about 7% over seven weeks. NAD+ levels showed 3-7% boosts from 5-amino-1MQ usage within 30 days without any changes in food intake—meaning mice maintained normal eating patterns while showing improved body composition regarding stored adipose tissue. Over six weeks, these mice exhibited various improvements including enhanced insulin sensitivity and increased action of factors like PPAR-alpha, a trigger for fat turnover and cell replication.

Source: Science Brief

Specialized lipids called FAHFAs (fatty acid hydroxyl fatty acids) provide improved insulin sensitivity and facilitate glucose entry into muscle cells through PPAR-alpha signaling. Most crucial evidence suggests that 5-amino-1MQ's effects may extend beyond its ability to downregulate NNMT and thus increase insulin action and glucose uptake into cells by: (1) increasing NAD+ molecules that may enable cells to produce an alternative class of lipids that have outstanding anti-diabetic and anti-inflammatory characteristics.

5-Amino-1MQ Impact on Muscle Function

The impact of 5-amino-1MQ on skeletal muscle is multifaceted. Much like in adipose tissue, this compound affects muscle energetics and may lead to the generation of mitochondria (power plants within cells creating energy).

Recent research suggests that inhibiting NNMT in any way, including with 5-amino-1MQ, may actually have direct effects on muscle structure and function.

Research in mice shows that after just four weeks, those treated with an NNMT inhibitor experienced considerable muscle cell activation within the body, activating muscle growth proteins. When treated with NNMT inhibition, these aging muscles were remarkably improved with increased muscle protein content—up to 70% in some cases. More tellingly, these changes started within days of 5-amino-1MQ administration, suggesting rapid activation of muscle-building processes even in diabetic animals.

These results showed elevated NAMPT levels, and reducing NNMT levels leads to more powerful effects on fat mass. By improving vitality and decreasing potential activation of sarcopenic (muscle-degrading) proteins such as ubiquitin ligase MuRF1, NNMT inhibition helps aging and diabetic animals maintain and repair muscle tissue. This stimulation helps individuals preserve their existing muscle mass, suggesting a potential role in treatment of conditions like muscular dystrophy and the muscle wasting that results from age.

The actual mechanisms by which NNMT inhibitors affect muscle function are not fully understood, but another factor appears to relate to NAD+ levels. Recall that NAD+ acts as a catalyst for various cellular processes. Compounds like 5-amino-1MQ have been shown to improve muscle function, heart pathologies, and IGF1 in several studies, in addition to metabolic effects seen in mice. These models and earlier studies suggest that 5-amino-1MQ's benefits, related to increases in NAD+ levels, represent one of several beneficial compound classes.

A Possible Role for 5-Amino-1MQ in Brain Function

NNMT is a critical compound in cellular energy expenditure. Depletion of NAD+ has been shown to produce impairment in brain energy activity, leading to decreased cognition. Studies show defects in neurogenesis (the development of new neurons) and reduced synaptic function at neuromuscular junctions where neurons connect to muscle fibers. Research in mice suggests that inhibition of NAD+ creates severe failure in various brain regions, leading to severe loss in cognitive function.

Though 5-amino-1MQ has not been specifically tested in this setting, there is good reason to believe that the compound, through its NAD+-related effects, may provide benefits. More significantly, there is evidence that restoration of NAD+ to neuronal structures creates improvements in cognitive dysfunction and potential increases in overall brain cognitive function. Studies also indicate brain health benefits, though comprehensive understanding remains to be established. There is active rationale for exploring the potential cognitive benefits of 5-amino-1MQ.

Significant research suggests that NNMT expression is increased in gastric cancer.

5-Amino-1MQ Conclusion

5-amino-1MQ is a groundbreaking compound that inhibits the enzyme nicotinamide N-methyltransferase. It has been shown in animal models to result in substantial weight reduction and preferential fat loss. NNMT is associated with metabolic diseases such as obesity and diabetes; therefore, inhibiting NNMT with 5-amino-1MQ can lead to weight reduction, diminished adiposity, and improved metabolic function. Laboratory animal research demonstrates that inhibiting NNMT with 5-amino-1MQ can lead to significant changes in body composition over the course of treatment—resulting in weight loss and improved muscle function. There is hope that compounds like 5-amino-1MQ may play a role in treating conditions like muscular dystrophy and age-related muscle wasting.

In summary, 5-amino-1MQ is a selective NNMT inhibitor with excellent promise as we continue to advance our understanding of obesity treatment and metabolic disease management.