Neuroprotective effects of leptin

[GinnyBerry]

A few days ago Dr. Michael Okun posted the attached article on his Twitter feed and said that he generally encourages his patients to be 5-10 lbs over their ideal weight.

Yoon, Seo Yeon et al. ‘Association Between Body Mass Index Changes and All-Cause Mortality in Parkinson’s Disease’. 1 Jan. 2024 : 1 – 10.

content.iospress.com/downlo...

The article is not completely compelling because the underweight groups are small in size, but it did make me pause. I'm low BMI, if not quite underweight and I have been losing weight.

I rationalized that it must be related to increased frailty and risks due to falls. So I dug in and it seems more than that. And it's complex. (And I'm only going to talk about leptin and not ghrelin).

This rather dense review on the non-appetite related functions of leptin suggest that leptin is neuroprotective.

ncbi.nlm.nih.gov/pmc/articl...

Leptin increases with higher BMI, and several studies show that leptin is lower in the Parkinson's groups.

I don't think I've heard a discussion about leptin here before. Certainly, gaining fat is not something that I have aimed to do or considered.

Between my lack of appetite, trying to get all my good nutrients, and my exercise regime, I'm pretty lean. Still, eating a little pizza every week sounds like pretty easy medicine .

I know many of you spend more time in the literature than me. Have you seen this? Thoughts?

[park_bear]

A word of caution interpreting these results - Association is not necessarily causation and people who should know better are often fooled. It's likely that those with advanced Parkinson's have trouble eating well and are underweight for that reason. In other words, low BMI is a result and not a cause of their condition.

See here for a related example: healthunlocked.com/cure-par...

[GinnyBerry in reply to park_bear]

yeah. I guess I was more interested in the role of leptin than I was the BMI..

There have been a lot of mouse studies looking at the role of leptin on preventing death of dopaminergic neurons. Leptin is stored in adipose tissue and levels are higher for individuals with more fat, for which BMI is a poor proxy (a main job of leptin is to signal about energy stores- so its primary function not just a correlation)

Here's another interesting review that points to its complex interactions-- and perhaps why it has not been targeted as a therapeutic.

sciencedirect.com/science/a...

[fnedorez70]

Food for thought: I used to lose weight no matter what I was eating. I have undergone ptt ablation and after the second side ablation I started gaining weight. I also got rid of the constipation. The sensitivity I had to thee animal protein and some fats is greatly diminished. The disease is still there and progressing faster than before.

[Juliegrace in reply to fnedorez70]

You’re progressing faster post PTT?

[Baron1]

I agree and have read about the hormones in the body / gut that can contribute to Neurological disorders.

There are a lot studies on Leptin and Ghrelin.

Here are some others:

independent.co.uk/news/heal...

sciencedirect.com/science/a...

There is a drug you can take:

Metreleptin injection is used together with a proper diet as replacement therapy to treat problems caused by leptin deficiency in patients with congenital or acquired generalized lipodystrophy.

Best Wishes

[GinnyBerry in reply to Baron1]

Thanks. Both the review on insulin and leptin and the reference to Harvey's work are very interesting.

It sounds like one challenge for a leptin therapy is getting it across the BBB (blood brain barrier) . That's always a challenge but leptin is a large molecule, which makes it even more difficult. The review also referenced a failed Phase 2/3 trial to use insulin delivery by inhalation to treat Alzheimer's. The authors believe it failed due to poor control over particle size by the device.

[sparkyparky]

I too have been losing weight without trying - down from a reasonably respectable 10 stone (140 lb ( I am 5'2") to just below 8 stone. I flagged this up a couple of years ago when I realised that I was losing muscle not fat. I am almost just skin and bones now - honestly my gave is lean and pinched, my arms are so skinny I had to buy a "small " cuff for the blood pressure machine and all my GP said was "well, you have a healthy bmi now" . Tests still being done

[Esperanto]

That a lower BMI is associated with higher PD mortality rates seems evident to me. The more severe your PD symptoms, the greater the weight loss often is, regardless of what I eat. However, this does not mean that weight loss is the cause of PD progression. On the contrary, a recent breakthrough in molecular genetics establishes a direct link between DNA damage and aging. It is suggested that aging results from the accumulation of DNA damages, particularly in long genes, which disrupt cellular functions. Good nutrition, caloric restriction, and fasting can help mitigate this damage, which in turn may lead to a slowdown of aging processes and the development of PD.