A Mechanism by Which Fat Causes Chronic Inflammation

A large weight of evidence shows that excess body fat - and specifically excess visceral fat - is bad for you in the long term. Put on weight and your life expectancy drops, even as your lifetime medical costs rise. You will most likely be less healthy for the rest of your life than your leaner peers, and they will outlive you. (Unless of course medical technology advances rapidly enough to save you from the consequences of your diet and lifestyle choices. But that's no certainty; why gamble when you don't have to?)

Some fraction of the consequences of being overweight are actually the consequences of a lack of regular exercise. After all, there is a strong correlation between gaining fat tissue and not exercising, and causal links between the two work both ways. Stop exercising without altering diet, and you'll gain fat tissue. On the flip side of the coin, gain enough fat tissue and exercising becomes much more of a challenge.

Another fraction of the consequences of being overweight stem from the low-level reactions of your metabolism to the overnutrition required to create that excess body fat - the reverse of dietary restriction, but something that is not as well researched at the level of cells and genes, despite the vast real-life population study in overfeeding taking place in much of the world these days. You might note research on harms caused by a dietary excess of methionine, however, methionine being one of the triggers for calorie restriction benefits when dietary intake is reduced. It swings the other way too.

The real monster when it comes to fat tissue and long term health appears to be inflammation, however. Temporary inflammation is a necessary portion of the response to damage and disease by the immune system, but chronic, unremitting inflammation accelerates progress towards frailty and ill-health. Indeed, it shows up as a contributing factor in degenerative aging later in life as the immune system becomes increasingly damaged and erratic. This process is known as inflammaging in some parts of the research community.

Distinct from the aging of the immune system, fat tissue itself spurs chronic inflammation. This has been known for some time, and researchers have been chasing down a detailed explanation as to why this is so. You might look at the connection to macrophage behavior, for example, or cytokine signaling. The more visceral fat you have, the higher your level of chronic inflammation - and thus the more damage gets added per unit time to the state of your biology. Aging itself is nothing more than damage and the reactions of bodily systems to that damage.

Here researchers present a fairly detailed account of how they think fat cells are causing this issue. You might look at the original paper as well as the more digestible research publicity materials linked below:

Obesity makes fat cells act like they're infected

High calorie diets cause [fat] cells to make major histocompatibility complex II, a group of proteins usually expressed to help the immune system fight off viruses and bacteria. In overweight mice and humans the fat cells, or adipocytes, are issuing false distress signals - they are not under attack by pathogens. But this still sends local immune cells into a tizzy, and that causes inflammation.

"We did not know fat cells could instigate the inflammatory response. That's because for a very long time we thought these cells did little else besides store and release energy. But what we have learned is that adipocytes don't just rely on local resident immune cells for protection - they play a very active role in their own defense. And that's not always a good thing."

Could the inflammation caused by a high fat diet serve any purpose, or is it a senseless response to an unnaturally caloric diet?

"The expression of MHCII in adipocytes does not seem to be helpful to the body. It is not at all clear what the advantage would be, given all the negative long-term consequences of fat tissue inflammation in people who are obese, including insulin resistance and, eventually, full diabetes. This just appears to be a runaway immune response to a modern high calorie diet. The bottom line is, you're feeding and feeding these fat cells and they're turning around and biting you back. They're doing the thing they're supposed to do - storing energy - but reacting negatively to too much of it."

[If researchers] can identify the antigen(s) that MHCII is presenting to T cells in fat tissue, medical researchers would have a new approach to target adipose inflammation in obese patients. The hypothesis is that if a treatment can interfere with the production or MHCII presentation of these antigens, this would reduce the activation of fat tissue immune cells and thus reduce inflammation.


Nice summary. It's unfortunate that the researchers make the (popular) assumption that "high fat diet" leads to high body fat, when in fact, it more likely leads to satiety and less overall calorie intake. They've conflated high body fat with dietary fat: "caused by high fat diet" -- no, its caused by excess body fat - what causes excess body fat is a separate question.

The real cause of excess body fat is much more likely to be excess dietary carbohydrate (sugars being the most dense form), which we see in the standard American diet. Excess carbohydrate consumption elevates insulin levels to abnormal levels, which in turn opens the fat cells to receiving more energy input, and does little to assuage satiety. After the blood sugar crash, once all of that extra glucose is transported into fat cells, typically one craves more food, despite already storing an excess of energy.

If you want references to the science behind Why We Get Fat, see the books of Gary Taubes.

Posted by: Brent Kearney at March 11th, 2013 12:01 PM


Surely one of the prime movers for obesity is a compromised gut flora and a reduction of the beneficial bacteria which allows carcinogens and other toxins to enter the blood stream causing the creation of excess fat tissue to be used as a toxic dumping ground. Another, is the inflamatory link caused between high levels of Omega 6 over Omega 3 fatty acids which excel pro inflamatory prostaglandin 2 hormone release caused by a diet high in breads sugars grains and high G.I. foods , Dairy and Trans fats, which activate Arachidonic Acid.

Obesity is the product of Low grade [silent] inflamation and as such should be treated as a Hormonal problem.

Posted by: will at February 1st, 2014 2:53 PM

Fat consumed can be stored in the adipose tissue exactly the way it was eaten.
It takes 3 calorie to convert fat to stored fat whereas it takes 23 calories to convert glucose to triglyceride and then store as fat in adipose tissue.
Actually one can have a biopsy of their fat tissue and it can be known where the fat came from, whether it was from a cow, pig, fish, sheep, chicken etc. The fat from the animal consumed is stored exactly the way it was eaten.
yes, fat makes you fat, and yes, REFINED CARBOHYDRATES, and processed food makes you fat but not COMPLEX CARBOHYDRATES FROM WHOLE PLANT FOOD. that nourishes the body and mind and maintain a healthy fauna and a strong immune.

Posted by: Georgie at January 15th, 2015 3:26 AM

As noted by Will, high intake of omega-6 (linoleic acid) promotes inflammation and obesity. Excerpt: "Just as all polyunsaturates are not created equal, all high fat diets are not created equal. A good example of this is an animal study we did where we compared three high fat diets. All with 60% of calories from fat, in mice. We compared high fat diets that resembled the linoleic acid, Omega 6 intakes, comparable to the levels at the beginning of the century, which was about 1 percent of calories, and those high fat diets with 8 percent of calories, more similar to the amount of Omega 6 in the diet simply from soy oil in the U-S diet, today. Moving from 1% to 8% linoleic acid in the mouse diets, not only tripled the levels of arachidonic acids, but also tripled the levels of a critical derivative of arachidonic acids, which is an endogenous cannabinoid, which creates a similar affect to marijuana. So it’s the brains own marijuana like molecules, and we were able to triple the body’s marijuana like hormones, three times higher in the liver and about 20% higher in the brains just by altering the linoleic acid in those two high-fat diets. Normally those high fat diets used for mice in studies are composed of high linoleic acid, found in soybean oil. When we deleted that one single molecule, the Omega 6 fatty acid, we were able to obliterate the ability of a 60% high fat diet to induce obesity in the mice...And we did it also in diets that were 35% of calories from fat, and also diets that were 12% of calories from fat. We were able to induce obesity in low fat diets, in the mice, by changing the bioactive properties of the fat, not just that it was high fat and more calories."


Posted by: David Brown at December 18th, 2015 1:13 AM

This is great information. Its a shame that this has not been broadcast more. For me the simple takeaway is to get adequate exercise, quit drinking calories, and eat foods that God made, not those that man made. I am more concerned with the quality of the calories I consume, not the quantity.

Posted by: Paul Dominy at November 28th, 2019 8:03 PM
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