Selegiline prevents weight gain on a high fat diet, increases UCP1

[Mauritio]

The good selegiline studies just keep on increasing in the last months. This one is really interesting. It showed that selegiline prevented weight gain on a high fat diet. On a normal diet it also lead to weight loss. The animals consumed more food ,and weighed less. Selegiline increased UCP1 and AMPK amongst others.

"The effect was evaluated through an assessment of body energy homeostasis, glucose tolerance tests, and biochemical analysis. Pharmacological inhibition of MAO-B by selegiline was observed to reduce body weight and fat accumulation, and improved glucose metabolism without a corresponding change in food intake, in HFD-fed obese mice. We also observed that both the expression of adipogenenic markers, including C/EBPα and FABP4, and lipogenic markers such as pACC were significantly reduced in epididymal white adipose tissues (eWATs). Conversely, increased expression of lipolytic markers such as ATGL and pHSL and AMPK phosphorylation were noted. Treating obese mice with selegiline significantly increased expression levels of UCP1 and promoted eWAT browning, indicating increased energy expenditure. These results suggest that selegiline, by inhibiting MAO-B activity, is a potential anti-obesity treatment."

In another study haidut posted selegiline was relatively ineffective for weight loss, the authors say that might be, because the central inhibition of MAO-B is much more effective than the peripheral inhibition, and apparently selegiline does not cross the BBB very effectively. In the case of this study they used very high doses (200mg HED) which might simply overpower the BBB and lead to a higher brain concentration. It might also be that it caused changes in the microbiome which another study has shown. It increased Akkermansia a lot which has been shown to lead to weight loss.

- Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice

 

[Charger]

Are you still taking 1.25mg once a week?

 

[Mauritio]

Are you still taking 1.25mg once a week?

Yes , not every week, but if I remember to do so. I really like it.

 

[cherrycherry]

Yes , not every week, but if I remember to do so. I really like it.

does selegiline has a long half life so doesn't need to take every day for the effect?

 

[Clyde]

I remember reading years ago that Selegiline loses it's selectivity for MAO-B at around 20mg and even at that small dose you can react to cheeses/chocolate because MAO-A breaks down tyramine.

But the point I wanted to make is that I don't know how they isolate the effect to MAO-B inhibition especially when Selegiline is inhibiting MAO-A at 200mg HED and also metabolized into amphetamines that could effect weight loss.

 

[ecstatichamster]

i take around 2mg or so daily and have for a year or so.

 

[Mauritio]

does selegiline has a long half life so doesn't need to take every day for the effect?

Not sure about the half life. But its an irreversible MAO-B inhibitor , it destroys the enzyme and I think it takes 2 weeks for them to fully recover.

 

[Mauritio]

I remember reading years ago that Selegiline loses it's selectivity for MAO-B at around 20mg and even at that small dose you can react to cheeses/chocolate because MAO-A breaks down tyramine.

But the point I wanted to make is that I don't know how they isolate the effect to MAO-B inhibition especially when Selegiline is inhibiting MAO-A at 200mg HED and also metabolized into amphetamines that could effect weight loss.

True, in high doses (MAO-A territory) it starts to have an "enhancer effect" ,which is how Knoll called it. So it might have to do with that.

"We found that selegiline possesses a dopaminergic enhancer effect: it stimulated the electrically induced [3H]dopamine release without influencing the resting [3H]dopamine release from rat striatal slices in 10-10-10-9 mol/L concentrations."
- Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline - PubMed.

Thats actually quite cool, ,because most substances that cause a dopamine release ,will lower your baseline dopamine level.
No free lunch, they say? Selegiline causes a dopamine release without affecting the baseline.

 

[haidut]

The good selegiline studies just keep on increasing in the last months. This one is really interesting. It showed that selegiline prevented weight gain on a high fat diet. On a normal diet it also lead to weight loss. The animals consumed more food ,and weighed less. Selegiline increased UCP1 and AMPK amongst others.

"The effect was evaluated through an assessment of body energy homeostasis, glucose tolerance tests, and biochemical analysis. Pharmacological inhibition of MAO-B by selegiline was observed to reduce body weight and fat accumulation, and improved glucose metabolism without a corresponding change in food intake, in HFD-fed obese mice. We also observed that both the expression of adipogenenic markers, including C/EBPα and FABP4, and lipogenic markers such as pACC were significantly reduced in epididymal white adipose tissues (eWATs). Conversely, increased expression of lipolytic markers such as ATGL and pHSL and AMPK phosphorylation were noted. Treating obese mice with selegiline significantly increased expression levels of UCP1 and promoted eWAT browning, indicating increased energy expenditure. These results suggest that selegiline, by inhibiting MAO-B activity, is a potential anti-obesity treatment."

In another study haidut posted selegiline was relatively ineffective for weight loss, the authors say that might be, because the central inhibition of MAO-B is much more effective than the peripheral inhibition, and apparently selegiline does not cross the BBB very effectively. In the case of this study they used very high doses (200mg HED) which might simply overpower the BBB and lead to a higher brain concentration. It might also be that it caused changes in the microbiome which another study has shown. It increased Akkermansia a lot which has been shown to lead to weight loss.

View attachment 58931

- Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice

Great study and a confirmation of this earlier research.

Inhibiting dopamine breakdown reverses obesity WITHOUT caloric restriction

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