Adiponectin

barbie

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SURPASS-2 study showed: "increases in total adiponectin (16-23% vs -.2%) with tirzepatide vs placebo"

Would you like to know more about adiponectin? I sure did. Especially with all the comments like "of course you loose weight if you eat less calories!" and "it just makes you eat less". I could tell from my own journey that WAY more than CICO (calories in, calories out) was occurring, kcal could NOT account for the speed of the weight loss! So here are the notes I took on my deep dive, they might bemmseen haphazard, but hopefully you can glean something useful. (I am not medical professional, and might be interpreting things incorrectly).

In short, adiponectin allows cells to burn fat for fuel more easily (lipolysis). And there is so much more! Read on.


○ Tirzepatide has been reported to increase levels of adiponectin, an adipokine involved in the regulation of both glucose and lipid metabolism, with a maximum increase of 26% from baseline after 26 weeks, at the 10 mg dosage. STUDY LINK: https://academic.oup.com/jcem/article/106/2/388/6000489?login=false)

○ metabolic syndrome often leads to left ventricular hypertrophy. low adiponectin is best predictor of LVH!

○ mice with increased adiponectin show reduced adipocyte differentiation (creation into fat cells... I think! need to dig deeper on this)

○ mice with increased adiponectin show increased energy expenditure associated with mitochondrial uncoupling. (I am *very* interested in the mitochondrial uncoupling! this is like burning "free" kcal, roughly). STUDY LINK: https://academic.oup.com/endo/article/148/4/1539/2501482?login=false

○ adiponectin suppresses the metabolic derangements that may result in:
*type 2 diabetes [pubmed.ncbi.nlm.nih.gov/12436346/]
*obesity
*atherosclerosis [pubmed.ncbi.nlm.nih.gov/12611609]
*non-alcoholic fatty liver disease (NAFLD)
*risk factor for metabolic syndrome
[https://pubmed.ncbi.nlm.nih.gov/19258676]

○ Adiponectin in combination with leptin has been shown to completely reverse insulin resistance in mice.[https://pubmed.ncbi.nlm.nih.gov/11479627]
○ coronary artery disease has been found to be positively associated with high molecular weight adiponectin, but not with low molecular weight adiponectin.[https://pubmed.ncbi.nlm.nih.gov/20398150]

○ Adiponectin exerts some of its weight reduction effects via the brain. This is similar to the action of leptin (in factb adiponectin and leptin can act synergistically) [https://pubmed.ncbi.nlm.nih.gov/11479627]

○ Adiponectin promoted synaptic and memory function in the brain. Humans with lower levels of adiponectin have reduced cognitive function.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340072]

○ Contrary to expectations, despite being produced in adipose (fat) tissue, adiponectin was found to be decreased in obesity (too many studies to list here). This downregulation has not been fully explained

○ Berberine, an isoquinoline alkaloid, has been shown to increase adiponectin expression, which partly explains its beneficial effects on metabolic disturbances. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788178]

○ Mice fed the omega-3 fatty acids (EPA and DHA) have shown increased plasma adiponectin. Curcumin, capsaicin, gingerol, and catechins also increase adiponectin expression.

○ adiponectin is low in Alzheimer’s [https://www.eurekalert.org/news-releases/538252]

○ Adiponectin reduces mitochondrial dysfunction (and reduces endothelial activation and pulmonary vascular injury) [https://faseb.onlinelibrary.wiley.com/doi/ftr/10.1096/fj.201901123R]
 
Here is a summary on adiponectin that I found elsewhere. I forgot to cite this list, so I do not know where I got it (research anything that looks interesting!)

ADIPONECTIN:
*decreased gluconeogenesis (glucose creation, in liver)

*increased glucose uptake [https://pubmed.ncbi.nlm.nih.gov/12611609]

*lipid catabolism (breakdown of fats) [https://pubmed.ncbi.nlm.nih.gov/12728641]

*β-oxidation [https://pubmed.ncbi.nlm.nih.gov/15544426]

*triglyceride clearance [https://pubmed.ncbi.nlm.nih.gov/15544426]

*protection from endothelial dysfunction (prevents atherosclerotic formation)

*insulin sensitivity

*weight loss

*control of energy metabolism [https://pubmed.ncbi.nlm.nih.gov/12728641]

*upregulation of uncoupling proteins [https://pubmed.ncbi.nlm.nih.gov/17204560]

*reduction of TNF-alpha (inflammatory cytokine)

*promotion of reverse cholesterol transport[43]
 
Interesting. I agree that this is clearly not calories in/out. I was a fat marathoner and triathlete on a diet gaining weight and wondering what was wrong with me.

Is anyone taking adeponedtin directly? If not, do you know why that wouldn't work or would be a bad idea?
 
Interesting. I agree that this is clearly not calories in/out. I was a fat marathoner and triathlete on a diet gaining weight and wondering what was wrong with me.

Is anyone taking adeponedtin directly? If not, do you know why that wouldn't work or would be a bad idea?
Interesting question!

I am not sure if there is a way to do that? I have not dug deep enough.

My initial thought is that there are still so many questions about adiponectin. One of them being: why aren't the increased adiponectin levels - seen in people with more adipose tissue - PROTECTIVE? Since adiponectin is so good, and adipose tissue is involved in its increase... why is it not reducing the adipose tissue in people releasing more adiponectin?

It reminds me of dopamine in Parkinson's. We know that increased dopamine is needed, and yet adding l-dopa (etc) does some good, while simultaneously hurting other parts of the brain. (I greatly simplified this). It is almost as thdasame organ can both be hurt and helped by the same substance. Which just shows how much we do NOT understand yet.

I will dig deeper on this. But honestly don't necessarily trust anything I come up with lol. 2 reasons: 1) just a mom, and 2) a recent study (ha ha) shows that perhaps half of all medical studies are either NOT reproducible by others... or are downright fraudulent. That really complicates things
 
So yes we know adiponectin is a hormone that's secreted by fat cells, and yes we know it plays a role in regulating metabolism and blood sugar levels.

However, some studies have found that people with type 2 diabetes and obesity tend to have lower levels of adiponectin, and that this can contribute to insulin resistance. So, the theory is that if GLP-1 users have higher levels of adiponectin, it could improve their insulin sensitivity and reduce the risk of diabetes-related complications. However, more research is needed to confirm this.

Source : "Impact of glucagon-like peptide-1 receptor agonists on adiponectin levels in patients with type 2 diabetes: A meta-analysis of randomized controlled trials".


This study looked at 20 different randomized controlled trials involving almost 1,500 people, and found that GLP-1 agonists led to a significant increase in adiponectin levels. The increase was about 0.59 micrograms per milliliter, which may not sound like a lot, but it's statistically significant.
 
Interesting. I agree that this is clearly not calories in/out. I was a fat marathoner and triathlete on a diet gaining weight and wondering what was wrong with me.

Is anyone taking adeponedtin directly? If not, do you know why that wouldn't work or would be a bad idea?


That's an excellent question! One reason is that adiponectin is a relatively new discovery, and it's not currently approved as a drug or supplement.

Another reason is that we still don't fully understand how adiponectin works in the body, or what the risks and benefits of taking it directly would be.

For now, the best way to increase adiponectin levels is through diet and exercise, or by taking medications like GLP-1 agonists that have been shown to increase adiponectin.
 
Interesting question!

I am not sure if there is a way to do that? I have not dug deep enough.

My initial thought is that there are still so many questions about adiponectin. One of them being: why aren't the increased adiponectin levels - seen in people with more adipose tissue - PROTECTIVE? Since adiponectin is so good, and adipose tissue is involved in its increase... why is it not reducing the adipose tissue in people releasing more adiponectin?

It reminds me of dopamine in Parkinson's. We know that increased dopamine is needed, and yet adding l-dopa (etc) does some good, while simultaneously hurting other parts of the brain. (I greatly simplified this). It is almost as thdasame organ can both be hurt and helped by the same substance. Which just shows how much we do NOT understand yet.

I will dig deeper on this. But honestly don't necessarily trust anything I come up with lol. 2 reasons: 1) just a mom, and 2) a recent study (ha ha) shows that perhaps half of all medical studies are either NOT reproducible by others... or are downright fraudulent. That really complicates things


’why aren't the increased adiponectin levels - seen in people with more adipose tissue - PROTECTIVE? Since adiponectin is so good, and adipose tissue is involved in its increase... why is it not reducing the adipose tissue in people releasing more adiponectin?’’


So, here's the thing: although adiponectin is associated with some beneficial effects, like lower levels of inflammation and better blood sugar control, it's not a magical cure-all for all the negative effects of excess body fat.

This is because body fat also releases other compounds that can have harmful effects on health, like pro-inflammatory cytokines and free fatty acids. So even if adiponectin levels are high, the body may still experience negative effects from the other things released by adipose tissue.

One of the other really interesting things about adiponectin is that it's not just released by adipose tissue - it's also released by skeletal muscle. In fact, some research suggests that adiponectin released by skeletal muscle may be even more important for metabolic health than adiponectin released by adipose tissue.

So, when someone is exercising and building muscle, they're not only burning calories and building strength, they're also increasing their levels of adiponectin and improving their metabolic health in multiple ways.
 
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