Article re: Immunity in adipose tissue
Cheesy567
Posts: 1,186 Member
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954849/pdf/nihms-531824.pdf
So, this isn't specifically LCHF related, but I figured some people here might be interested. An article citing this review popped up on one of my RSS feeds for a treatment I take for an autoimmune disease. It was the first I heard of the variations in cellular immunity seen between obese adipose tissue (which is predominately populated with pro-inflammatory immune cells) and lean adipose tissue (predominately populated with regulatory immune cells).
Pretty heavy reading for non-immunologists, myself included, so plan some time if you want to read it in-depth.
But, it was the easiest yet comprehensive review article I could find.
There are articles/ studies building off these concepts proposing an autoimmune cause of insulin resistance and obesity, and studies in mice looking at treatment of obesity with targeted immune therapies such as anti-CD20 antibodies, natural killer cell targets, and various complement factors (IL4, IL10 are a couple that I saw in a very brief scroll today).
Combined with the growing knowledge of the impact of dietary sugars on systemic inflammation, it makes me wonder if the success of LCHF in treating T2D runs deeper than ketoadaptation, fat burning, and appetite suppression... Perhaps it's impacting the underlying cause of obesity and IR...
So, this isn't specifically LCHF related, but I figured some people here might be interested. An article citing this review popped up on one of my RSS feeds for a treatment I take for an autoimmune disease. It was the first I heard of the variations in cellular immunity seen between obese adipose tissue (which is predominately populated with pro-inflammatory immune cells) and lean adipose tissue (predominately populated with regulatory immune cells).
Pretty heavy reading for non-immunologists, myself included, so plan some time if you want to read it in-depth.
But, it was the easiest yet comprehensive review article I could find.
There are articles/ studies building off these concepts proposing an autoimmune cause of insulin resistance and obesity, and studies in mice looking at treatment of obesity with targeted immune therapies such as anti-CD20 antibodies, natural killer cell targets, and various complement factors (IL4, IL10 are a couple that I saw in a very brief scroll today).
Combined with the growing knowledge of the impact of dietary sugars on systemic inflammation, it makes me wonder if the success of LCHF in treating T2D runs deeper than ketoadaptation, fat burning, and appetite suppression... Perhaps it's impacting the underlying cause of obesity and IR...
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Another review that explains the major cells involved, if you're not familiar with the terminology it might give a bit better background for you.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041712/pdf/nihms-585037.pdf1 -
Thanks for posting this. A bit heavy but I will make time.1
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Very Interesting, article is looking at the very point which is the beginning of a person becoming obese.......this leptin, adipose tissue and fat connection---but have to wonder if MINUS simple sugars and simple carbs, the same questions would be of any validity?0
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have to wonder if MINUS simple sugars and simple carbs, the same questions would be of any validity?
Good question, and I have similar questions.
Why is adipose associated with inflammation?
Why would inflammation be a bad thing? It's a sign of healing, right?
I've looked into this a little bit, and I couldn't find any great answers, so I can only speculate.
It's not the inflammation that's bad per se, but it's an indication that there's something the body is trying to heal. So the body thinks there's damage, or an infection, or something.
In the case of high blood sugar, there may be real damage. For example, nerve damage or endothelial damage.
It's the endothelial damage and resulting clotting that Malcom Kendrick believes is responsible for CVD:
https://drmalcolmkendrick.org/
In the case of fat, there are a couple of theories (probably more). One is that the inflammation response is needed for adipose tissue remodeling. I.e., it's a healthy response to building larger fat stores.
Another, and one that I find more interesting, is that it's a result of chronic excess calories coming in too fast for the body to build sufficient fat stores. For example, adipose tissue is growing faster than the vasculature needed to support it. So the fat cells die, and the inflammation response is generated to clear up the mess.
Still, that doesn't explain why the inflammation of fat would be associated with poor health. But if you're in a chronic state of excess caloric intake, your ectopic fat (e.g., organ fat) is also increasing, and that would give us an actual mechanism of damage.
TL;DR: It's chronic excess consumption that slowly kills us. If you're in a state of losing weight, inflammation should be lower.4 -
Very Interesting, article is looking at the very point which is the beginning of a person becoming obese.......
Exactly-- where is the switch flipping that turns off the typical satiety mechanisms? And why? Yes, there's extra calories coming in, but it's resulting in continued or more hunger, a sign of breakdown of the satiety signaling. (All theories, I'm not insinuating that this article is proving it)but have to wonder if MINUS simple sugars and simple carbs, the same questions would be of any validity?
Not quite sure what you mean, could you clarify? Do you mean the initial onset of obesity wouldn't happen in a setting without simple sugars/carbs?0 -
Good question, and I have similar questions.
Why is adipose associated with inflammation?
Why would inflammation be a bad thing? It's a sign of healing, right?
It's a mechanism of healing, but it's actually the means with which the body gets rid of damage-- i.e. It's destructive / catabolic, and not building/renewing/ anabolic. This is the type of inflammation seen in Rheumatoid Arthritis, destroying the joints and connective tissue. The type of inflammation seen in Multiple Sclerosis, destroying nerves.
It's a dysregulated immune response, one that's revved up, out of control. It's more like cancer (dysregulated cell growth into tumors) than healing (normal proliferation of cells to facilitate tissue repair). It's the loss of regulation and mid-guided targets that cause the pathology of the disease. The body isn't fighting an invader, it's fighting itself.
(Keep in mind that autoimmunity is a beastly complicated subject, not one I am an expert of. My understanding may be wrong. Please correct me if you're understanding is more complete than mine! However, there is no doubt that dysregulated inflammatory states are associated with autoimmune disorders, in fact one could say that autoimmunity and inflammation go hand-in-hand.)
The cells they're describing are immune cells, found in all tissues of the body and in the blood stream. It's not that they're trying to connect
The article is talking about how adipose tissue varies between lean people and obese people. (Citing research done in animals and people) It's looking at the difference in immune cells found in the adipose tissue. Lean people' adipose tends to have immune cells that down-regulate inflammation. Obese people's adipose tends to have immune cells that up-regulate inflammation, while having fewer of the down-regulating cells present.
What really caught my attention was the research (in obese mice models) using treatments developed for lymphoma that are used for many autoimmune disorders. They found that it impacted obesity, insulin resistance, and development of Type 2 Diabetes. They're successfully treating obese mice as if they have an autoimmune disorder, and seeing improvements in these metabolic disorders.3 -
TL;DR: It's chronic excess consumption that slowly kills us. If you're in a state of losing weight, inflammation should be lower.
They're looking at it from the other way-- does chronic dysregulated inflammation lead to changes in the adipose signaling pathways, which in turn drive people to eat beyond satiety and become obese?
And, they're identifying targets that might be potential ways to treat obesity-- correct the signaling pathway, and weight might correct itself.
I was just scanning the articles I was reviewing this morning, but it looks like there are groups researching potential targets to use as vaccines to prevent and/or treat these metabolic disorders.
TL;DR: Obesity may be a treatable disease, not a character flaw.2 -
They're looking at it from the other way-- does chronic dysregulated inflammation lead to changes in the adipose signaling pathways, which in turn drive people to eat beyond satiety and become obese?
Understood. But that's the problem I have with a lot of bottom-up science. They are making some interesting observations, but I like to try to fit those observations into a top-down framework that makes sense in terms of evolution or non-pathological physiology. It saves me from getting lost in the minutia.
I'll re-read the papers to see what I missed, but my current mental model is that hyperinsulinemia is one of the first steps in a long cascade. The first paper is suggesting that insulin resistance is a side-effect of obesity, but there's a lot of data that suggests that insulin resistance can come well before one becomes obese.
In your case, I assume that anything you can do to quiet your immune system (without compromising useful immunity) is a Good Thing.2 -
Understood. But that's the problem I have with a lot of bottom-up science. They are making some interesting observations, but I like to try to fit those observations into a top-down framework that makes sense in terms of evolution or non-pathological physiology. It saves me from getting lost in the minutia.
Right-- standing on ones head gives both a new perspective and an uncomfortable head rushI'll re-read the papers to see what I missed, but my current mental model is that hyperinsulinemia is one of the first steps in a long cascade. The first paper is suggesting that insulin resistance is a side-effect of obesity, but there's a lot of data that suggests that insulin resistance can come well before one becomes obese.
I have to read it again, too. My initial take-home message was one of a common inflammatory "light switch" that turned the regulation haywire, and that the IR and obesity co-arise. (I didn't get the sense of causality- that obesity caused the inflammation leading to the metabolic issues, rather only a sense of correlation)
But I agree that there's a lot of evidence that IR precedes obesity-- there are also cases of thin people who are IR and obese people who are not. I think it's still an area of medicine that is more complex than we ever thought. I'm glad there's research coming at it from all angles... Not just CICO, you know?
Indeed. ThanksIn your case, I assume that anything you can do to quiet your immune system (without compromising useful immunity) is a Good Thing.
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Fat is not passive. It's inflammatory.One key change in adipose tissue during obesity is an increase in the percentage of macrophages resident within the tissue. Macrophages are a primary source of pro-inflammatory cytokines secreted by adipose tissue.
http://themedicalbiochemistrypage.org/adipose-tissue.php
...and what helps clear out protein debris and junk?...drumroll...autophagy!1 -
Interesting..... bump. I wonder what the correlation of adipose tissue/inflammatory response is (if any) in other autoimmune conditions....1
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